{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:36:31Z","timestamp":1786448191526,"version":"build-2736575974"},"reference-count":276,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>RNA therapeutics have evolved from passive genetic intermediaries into highly programmable platforms, fundamentally transforming the landscape of precision medicine. This comprehensive review examines the molecular architecture and mechanisms of established platforms in the clinical setting, including mRNA, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs) and aptamers, alongside next-generation platforms, such as CRISPR-guided systems and circular RNAs (circRNAs). Moreover, we discuss strategies to overcome systemic delivery bottlenecks and evaluate advanced non-viral systems, emphasizing lipid nanoparticles (LNPs), polymers and tissue-specific ligand conjugates that facilitate precise intracellular targeting. Furthermore, we explore the clinical expansion of these platforms across infectious diseases, rare genetic disorders, oncology and cardiovascular conditions. Finally, we highlight how the integration of artificial intelligence (AI) and machine learning (ML) redefines the limits of individualized, programmable RNA therapies by accelerating sequence optimization and nanoparticle formulation.<\/jats:p>","DOI":"10.3390\/cimb48080809","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:32:16Z","timestamp":1786444336000},"page":"809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-6076","authenticated-orcid":false,"given":"Konstantina","family":"Athanasopoulou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glykeria N.","family":"Daneva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3984-3324","authenticated-orcid":false,"given":"Vasiliki-Ioanna","family":"Michalopoulou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Stamelou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-2278","authenticated-orcid":false,"given":"Panagiotis","family":"Tsiakanikas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-357X","authenticated-orcid":false,"given":"Panagiotis G.","family":"Adamopoulos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1718","DOI":"10.1002\/wrna.1718","article-title":"The Central Dogma revisited: Insights from protein synthesis, CRISPR, and beyond","volume":"13","author":"Ille","year":"2022","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jconrel.2019.05.032","article-title":"Therapeutic mRNA delivery to leukocytes","volume":"305","author":"Kon","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1124\/pr.120.019554","article-title":"RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges","volume":"72","author":"Yu","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Batista-Duharte, A., Sendra, L., Herrero, M.J., Tellez-Martinez, D., Carlos, I.Z., and Alino, S.F. (2020). Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement. Biomolecules, 10.","DOI":"10.3390\/biom10020316"},{"key":"ref_5","first-page":"14","article-title":"Fomivirsen approved for CMV retinitis","volume":"4","author":"Roehr","year":"1998","journal-title":"J. Int. Assoc. Physicians AIDS Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1358\/dot.2001.37.4.620590","article-title":"Fomivirsen","volume":"37","author":"Grillone","year":"2001","journal-title":"Drugs Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-0716-1298-9_1","article-title":"RNA Interference: Story and Mechanisms","volume":"Volume 2282","author":"Sioud","year":"2021","journal-title":"Design and Delivery of SiRNA Therapeutics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/s41587-023-02105-y","article-title":"RNA interference in the era of nucleic acid therapeutics","volume":"42","author":"Jadhav","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_9","first-page":"570","article-title":"FDA approves patisiran to treat hereditary transthyretin amyloidosis","volume":"14","author":"Wood","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","first-page":"101121","article-title":"The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines","volume":"21","author":"Lin","year":"2026","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1690918","article-title":"Direct gene transfer into mouse muscle in vivo","volume":"247","author":"Wolff","year":"1990","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1038\/mt.2008.200","article-title":"Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability","volume":"16","author":"Kariko","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Morais, P., Adachi, H., and Yu, Y.T. (2021). The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.789427"},{"key":"ref_14","first-page":"194","article-title":"Nusinersen: A Novel Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy","volume":"24","author":"Neil","year":"2019","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1016\/j.neuron.2023.05.027","article-title":"Antisense drugs for rare and ultra-rare genetic neurological diseases","volume":"111","author":"McCauley","year":"2023","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vallet, T., and Vignuzzi, M. (2025). Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development. Viruses, 17.","DOI":"10.3390\/v17040566"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhao, Y.Y., Zhu, F.M., Zhang, Y.J., and Wei, H.Y. (2025). Harnessing the Loop: The Perspective of Circular RNA in Modern Therapeutics. Vaccines, 13.","DOI":"10.3390\/vaccines13080821"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41392-022-01007-w","article-title":"mRNA-based therapeutics: Powerful and versatile tools to combat diseases","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Makkar, S.K. (2025). Advances in RNA-based therapeutics: Current breakthroughs, clinical translation, and future perspectives. Front. Genet., 16.","DOI":"10.3389\/fgene.2025.1675209"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102717","DOI":"10.1016\/j.omtn.2025.102717","article-title":"Exploring CRISPR-Cas: The transformative impact of gene editing in molecular biology","volume":"36","author":"Pandey","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102733","DOI":"10.1016\/j.omtn.2025.102733","article-title":"Precision gene editing: The power of CRISPR-Cas in modern genetics","volume":"36","author":"Joo","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e17029","DOI":"10.1002\/advs.202417029","article-title":"From Code to Life: The AI-Driven Revolution in Genome Editing","volume":"12","author":"Li","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1002\/eji.1830230749","article-title":"Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA","volume":"23","author":"Martinon","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA","volume":"23","author":"Kariko","year":"2005","journal-title":"Immunity"},{"key":"ref_25","first-page":"523","article-title":"Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: Implication for therapeutic RNA development","volume":"10","author":"Kariko","year":"2007","journal-title":"Curr. Opin. Drug Discov. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.jconrel.2021.03.043","article-title":"The dawn of mRNA vaccines: The COVID-19 case","volume":"333","author":"Verbeke","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9015","DOI":"10.1007\/s12274-024-6978-6","article-title":"mRNA medicine: Recent progresses in chemical modification, design, and engineering","volume":"17","author":"Hou","year":"2024","journal-title":"Nano Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/s41392-024-02002-z","article-title":"Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications","volume":"9","author":"Shi","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108015","DOI":"10.1016\/j.jbc.2024.108015","article-title":"mRNA vaccine sequence and structure design and optimization: Advances and challenges","volume":"301","author":"Jin","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102721","DOI":"10.1016\/j.omtn.2025.102721","article-title":"mRNA therapeutics: Transforming medicine through innovation in design, delivery, and disease treatment","volume":"36","author":"Ige","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/nrm.2017.103","article-title":"Functional 5\u2032 UTR mRNA structures in eukaryotic translation regulation and how to find them","volume":"19","author":"Leppek","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kirshina, A., Vasileva, O., Kunyk, D., Seregina, K., Muslimov, A., Ivanov, R., and Reshetnikov, V. (2023). Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA. Biomolecules, 13.","DOI":"10.3390\/biom13111677"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2311752120","DOI":"10.1073\/pnas.2311752120","article-title":"Monovalent SARS-CoV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants","volume":"120","author":"Ye","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1073\/pnas.1515152113","article-title":"Structural basis for m7G recognition and 2\u2032-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I","volume":"113","author":"Devarkar","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9051","DOI":"10.1093\/nar\/gkac722","article-title":"2\u2032-O-Methylation of the second transcribed nucleotide within the mRNA 5\u2032 cap impacts the protein production level in a cell-specific manner and contributes to RNA immune evasion","volume":"50","author":"Drazkowska","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e202500826","DOI":"10.1002\/cmdc.202500826","article-title":"The 5\u2032 Cap Epitranscriptome and Beyond: Natural and Engineered 5\u2032 Cap Modifications for Optimizing mRNA Therapeutics and Functional Studies","volume":"21","author":"Dahm","year":"2026","journal-title":"ChemMedChem"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Heendeniya, S.N., Chen, S., Bhatti, S., Zahra, Q.U.A., Rahimizadeh, K., Poudel, B.H., Wilton, S.D., and Veedu, R.N. (2025). Beginning of a new era of synthetic messenger RNA therapeutics: Comprehensive insights on mRNA drug design, development and applications. Exp. Biol. Med., 250.","DOI":"10.3389\/ebm.2025.10784"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1186\/s40001-025-03060-x","article-title":"Research progress of mRNA vaccines for infectious diseases","volume":"30","author":"Zhang","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vishweshwaraiah, Y.L., and Dokholyan, N.V. (2022). mRNA vaccines for cancer immunotherapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1029069"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Vavilis, T., Stamoula, E., Ainatzoglou, A., Sachinidis, A., Lamprinou, M., Dardalas, I., and Vizirianakis, I.S. (2023). mRNA in the Context of Protein Replacement Therapy. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010166"},{"key":"ref_41","first-page":"118","article-title":"The mRNA-Based Innovative Strategy: Progress and Challenges","volume":"18","author":"Zhou","year":"2026","journal-title":"Nanomicro Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e20230036","DOI":"10.1002\/INMD.20230036","article-title":"mRNA-based chimeric antigen receptor T cell therapy: Basic principles, recent advances and future directions","volume":"2","author":"Xiao","year":"2024","journal-title":"Interdiscip. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, Y., Ou, Y., and Hou, L. (2024). Advances in RNA-Based Therapeutics: Challenges and Innovations in RNA Delivery Systems. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47010022"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10529-026-03713-9","article-title":"Antisense oligonucleotides: Targeting oncogenic long non-coding RNAs for cancer therapy","volume":"48","author":"Irandoost","year":"2026","journal-title":"Biotechnol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrneurol.2017.148","article-title":"Antisense oligonucleotides: The next frontier for treatment of neurological disorders","volume":"14","author":"Rinaldi","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Szukowska, A., Zuk, M., Sztompke, J., Bednarz, B., and Kazmierczak, U. (2025). Application of Antisense Oligonucleotides as an Alternative Approach for Gene Expression Control and Functional Studies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110524"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100016","DOI":"10.1016\/j.premed.2025.100016","article-title":"Advances in RNA therapeutics: Classes, innovations and clinical applications","volume":"3","author":"Shahid","year":"2025","journal-title":"J. Precis. Med. Health Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cmet.2018.03.004","article-title":"RNA-Targeted Therapeutics","volume":"27","author":"Crooke","year":"2018","journal-title":"Cell Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1594","DOI":"10.1002\/wrna.1594","article-title":"The powerful world of antisense oligonucleotides: From bench to bedside","volume":"11","author":"Quemener","year":"2020","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1093\/nar\/gkz247","article-title":"Site-specific replacement of phosphorothioate with alkyl phosphonate linkages enhances the therapeutic profile of gapmer ASOs by modulating interactions with cellular proteins","volume":"47","author":"Migawa","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1002\/cbdv.201100081","article-title":"An overview of sugar-modified oligonucleotides for antisense therapeutics","volume":"8","author":"Prakash","year":"2011","journal-title":"Chem. Biodivers."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/dvg.20689","article-title":"Use of fully modified 2\u2032-O-methyl antisense oligos for loss-of-function studies in vertebrate embryos","volume":"49","author":"Schneider","year":"2011","journal-title":"Genesis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e265","DOI":"10.1038\/mtna.2015.39","article-title":"Evaluation of 2\u2032-Deoxy-2\u2032-fluoro Antisense Oligonucleotides for Exon Skipping in Duchenne Muscular Dystrophy","volume":"4","author":"Jirka","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nbt.3765","article-title":"The chemical evolution of oligonucleotide therapies of clinical utility","volume":"35","author":"Khvorova","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102224","DOI":"10.1016\/j.omtn.2024.102224","article-title":"Unlocking the therapeutic potential of locked nucleic acids through lipid nanoparticle delivery","volume":"35","author":"Qassem","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s40291-021-00573-z","article-title":"Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension","volume":"26","author":"Yasuhara","year":"2022","journal-title":"Mol. Diagn. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s40259-024-00665-2","article-title":"Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs","volume":"38","author":"Sang","year":"2024","journal-title":"BioDrugs"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1093\/nar\/gku184","article-title":"Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides","volume":"42","author":"Ward","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13096","DOI":"10.1039\/D5SC03751D","article-title":"Engineering antisense oligonucleotides for targeted mRNA degradation through lysosomal trafficking","volume":"16","author":"Kashyap","year":"2025","journal-title":"Chem. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.omtn.2023.04.010","article-title":"Block or degrade? Balancing on- and off-target effects of antisense strategies against transcripts with expanded triplet repeats in DM1","volume":"32","author":"Willemse","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40824-022-00292-4","article-title":"Nonviral delivery systems for antisense oligonucleotide therapeutics","volume":"26","author":"Huang","year":"2022","journal-title":"Biomater. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s44386-025-00037-y","article-title":"Advancements in RNA-based therapies from bench to bedside","volume":"3","author":"Singh","year":"2026","journal-title":"npj Drug Discov."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1093\/nar\/gkv275","article-title":"Splice-shifting oligonucleotide (SSO) mediated blocking of an exonic splicing enhancer (ESE) created by the prevalent c.903+469T>C MTRR mutation corrects splicing and restores enzyme activity in patient cells","volume":"43","author":"Palhais","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s40259-024-00644-7","article-title":"Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases","volume":"38","author":"Chen","year":"2024","journal-title":"BioDrugs"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1038\/s41467-020-17093-9","article-title":"Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression","volume":"11","author":"Lim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Xu, L., Zhang, H., Jiang, B., Jiang, Y., and Lu, H. (2026). Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers. Pharmaceutics, 18.","DOI":"10.20944\/preprints202603.1165.v1"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11031","DOI":"10.3390\/cimb46100655","article-title":"Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications","volume":"46","author":"Malinowska","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"W39","DOI":"10.1093\/nar\/gkaf392","article-title":"ASOptimizer: Optimizing chemical diversity of antisense oligonucleotides through deep learning","volume":"53","author":"Kang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"W193","DOI":"10.1093\/nar\/gkab442","article-title":"eSkip-Finder: A machine learning-based web application and database to identify the optimal sequences of antisense oligonucleotides for exon skipping","volume":"49","author":"Chiba","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/35888","article-title":"Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans","volume":"391","author":"Fire","year":"1998","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1096\/fj.06-6014rev","article-title":"A brief history of RNAi: The silence of the genes","volume":"20","author":"Sen","year":"2006","journal-title":"FASEB J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.devcel.2011.01.012","article-title":"The many faces of RNAi","volume":"20","author":"Ketting","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.omtn.2023.07.018","article-title":"25 years of maturation: A systematic review of RNAi in the clinic","volume":"33","author":"Corydon","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1124\/jpet.122.001234","article-title":"RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies","volume":"384","author":"Traber","year":"2023","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1126\/science.1073827","article-title":"A microRNA in a multiple-turnover RNAi enzyme complex","volume":"297","author":"Hutvagner","year":"2002","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.cell.2009.01.035","article-title":"Origins and Mechanisms of miRNAs and siRNAs","volume":"136","author":"Carthew","year":"2009","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev-biophys-083012-130404","article-title":"Molecular mechanisms of RNA interference","volume":"42","author":"Wilson","year":"2013","journal-title":"Annu. Rev. Biophys."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7605","DOI":"10.2147\/IJN.S436038","article-title":"A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy","volume":"18","author":"Zhang","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1038\/mtna.2015.23","article-title":"siRNA Versus miRNA as Therapeutics for Gene Silencing","volume":"4","author":"Lam","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jim.2015.07.006","article-title":"Direct uptake of Antagomirs and efficient knockdown of miRNA in primary B and T lymphocytes","volume":"426","author":"Haftmann","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1093\/nar\/gkae141","article-title":"Chemical modification patterns for microRNA therapeutic mimics: A structure-activity relationship (SAR) case-study on miR-200c","volume":"52","author":"Garreau","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","article-title":"Therapeutic siRNA: State of the art","volume":"5","author":"Hu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"102437","DOI":"10.1016\/j.omtn.2024.102437","article-title":"Development, opportunities, and challenges of siRNA nucleic acid drugs","volume":"36","author":"Xiao","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1186\/s12951-023-02147-z","article-title":"Engineering siRNA therapeutics: Challenges and strategies","volume":"21","author":"Fatima","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"Genome editing. The new frontier of genome engineering with CRISPR-Cas9","volume":"346","author":"Doudna","year":"2014","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41580-026-00969-x","article-title":"Molecular mechanisms and biotechnology applications of CRISPR\u2013Cas12a","volume":"27","author":"Saha","year":"2026","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Larsen, B.B., Kimchi, O., Dunkley, O.R.S., Grimm, M.S., Siegers, J.Y., Huang, Y., Vandavasi, V.G., Nguyen, L.T., Lamb, C.H., and Aranovich, I. (2025). RNA structure modulates Cas13 activity and enables mismatch detection. Nat. Biotechnol., online ahead of print.","DOI":"10.1038\/s41587-025-02868-6"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kang, K., Song, Y., Kim, I., and Kim, T.J. (2022). Therapeutic Applications of the CRISPR-Cas System. Bioengineering, 9.","DOI":"10.3390\/bioengineering9090477"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2635868","DOI":"10.1080\/21645515.2026.2635868","article-title":"Current landscape of clinical trials for mRNA-based therapeutics","volume":"22","author":"Li","year":"2026","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102636","DOI":"10.1016\/j.omtn.2025.102636","article-title":"Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges","volume":"36","author":"Kalter","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ewaisha, R., and Anderson, K.S. (2023). Immunogenicity of CRISPR therapeutics-Critical considerations for clinical translation. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1138596"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7208","DOI":"10.1038\/s41467-025-62606-z","article-title":"The hidden risks of CRISPR\/Cas: Structural variations and genome integrity","volume":"16","author":"Aussel","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Ugwu, O.P., Okon, M.B., Ogenyi, F.C., Ugwu, J.N., and Ugwu, C.N. (2026). Circular RNA therapeutics: A new class of long-acting RNA medicines for oncology, immunology, and rare diseases. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1758902"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s44258-026-00079-5","article-title":"Unlocking the potential of engineered circular RNA therapeutics","volume":"4","author":"Zhen","year":"2026","journal-title":"Med-X"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ymthe.2025.10.038","article-title":"CircRNA: Unlocking new frontiers in therapeutic and vaccine development","volume":"34","author":"Bahrulolum","year":"2026","journal-title":"Mol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e20240044","DOI":"10.1002\/EXP.20240044","article-title":"Exploring the Potential and Advancements of Circular RNA Therapeutics","volume":"5","author":"Wang","year":"2025","journal-title":"Exploration"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"102687","DOI":"10.1016\/j.omtn.2025.102687","article-title":"The potential and challenges of circular RNA in the development of vaccines and drugs for emerging infectious diseases","volume":"36","author":"Chen","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Sun, Y., Zhang, Y., Chen, W., Chen, T., Zhang, Y., Zhang, S., and Lu, C. (2026). Enhancing Circular RNA Translation Efficiency Through Dual Internal Ribosome Entry Sites. Biology, 15.","DOI":"10.3390\/biology15040317"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41541-025-01097-x","article-title":"Recent advances and perspectives on the development of circular RNA cancer vaccines","volume":"10","author":"Gong","year":"2025","journal-title":"npj Vaccines"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Shanaa, O.A., Rumyantsev, A., Sambuk, E., and Padkina, M. (2021). In Vivo Production of RNA Aptamers and Nanoparticles: Problems and Prospects. Molecules, 26.","DOI":"10.3390\/molecules26051422"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.omtn.2022.07.012","article-title":"Minding the gap: Unlockingthe therapeutic potentialof aptamers and making up for lost time","volume":"29","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.ymthe.2025.02.047","article-title":"Using aptamers for targeted delivery of RNA therapies","volume":"33","author":"Driscoll","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ymthe.2024.01.028","article-title":"Current RNA strategies in treating cardiovascular diseases","volume":"32","author":"Chia","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41419-022-05075-2","article-title":"RNA-based therapeutics: An overview and prospectus","volume":"13","author":"Zhu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e70180","DOI":"10.1002\/mco2.70180","article-title":"Aptamers: Design, Theory, and Applications to Diagnosis and Therapy for Diseases","volume":"6","author":"Hassibian","year":"2025","journal-title":"MedComm"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Santarpia, G., and Carnes, E. (2024). Therapeutic Applications of Aptamers. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202405.1428.v1"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e02954","DOI":"10.1002\/slct.202502954","article-title":"The Application of Aptamers in Pharmacological Drug Development and Therapeutic","volume":"10","author":"Pavlova","year":"2025","journal-title":"ChemistrySelect"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"101350","DOI":"10.1016\/j.mam.2025.101350","article-title":"The recent blooming of therapeutic aptamers","volume":"102","author":"Cesarini","year":"2025","journal-title":"Mol. Asp. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"119299","DOI":"10.1016\/j.biopha.2026.119299","article-title":"Aptamers in cancer therapy: Why has clinical translation lagged behind preclinical promise?","volume":"198","author":"Tran","year":"2026","journal-title":"Biomed. Pharmacother."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Kumar Kulabhusan, P., Hussain, B., and Yuce, M. (2020). Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070646"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.1021\/acs.chemrev.1c00009","article-title":"Thermostability, Tunability, and Tenacity of RNA as Rubbery Anionic Polymeric Materials in Nanotechnology and Nanomedicine-Specific Cancer Targeting with Undetectable Toxicity","volume":"121","author":"Binzel","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Pozdniakova, N., Generalov, E., Shevelev, A., and Tarasova, O. (2025). RNA Therapeutics: Delivery Problems and Solutions-A Review. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17101305"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"13301","DOI":"10.1021\/acs.chemrev.4c00472","article-title":"Technologies for Targeted RNA Degradation and Induced RNA Decay","volume":"124","author":"Mikutis","year":"2024","journal-title":"Chem. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/mt.2009.91","article-title":"The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice","volume":"17","author":"Gao","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ymthe.2024.01.005","article-title":"The landscape of nanoparticle-based siRNA delivery and therapeutic development","volume":"32","author":"Moazzam","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e70010","DOI":"10.1002\/wnan.70010","article-title":"Nano Approaches to Nucleic Acid Delivery: Barriers, Solutions, and Current Landscape","volume":"17","author":"Gonzalez","year":"2025","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/psp4.70108","article-title":"Modeling and Simulation Identifies Endocytosis Uptake Rate and Fraction Unbound as Important Predictors of Oligonucleotide Pharmacokinetics","volume":"14","author":"Stader","year":"2025","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Carton-Garcia, F., Saande, C.J., Meraviglia-Crivelli, D., Aldabe, R., and Pastor, F. (2021). Oligonucleotide-Based Therapies for Renal Diseases. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030303"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Peng, M., Fang, F., and Wang, B. (2025). Nanoparticle technologies for liver targeting and their applications in liver diseases. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1661872"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1021\/acsnano.5c21857","article-title":"Mechanistic and Strategic Insights into How Lipid Nanoparticles Interact with Membrane-Based Biological Barriers","volume":"20","author":"Zhao","year":"2026","journal-title":"ACS Nano"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11095-023-03471-7","article-title":"Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells","volume":"40","author":"Liu","year":"2023","journal-title":"Pharm. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.1002\/jps.21270","article-title":"Nanovehicular intracellular delivery systems","volume":"97","author":"Prokop","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"103761","DOI":"10.1016\/j.cis.2025.103761","article-title":"The surface-first paradigm: Engineering nanocarriers for infection-responsive drug delivery","volume":"349","author":"Shah","year":"2026","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1021\/acsnano.5c18112","article-title":"The Biology of Endosomal Escape: Strategies for Enhanced Delivery of Therapeutics","volume":"20","author":"Chahal","year":"2026","journal-title":"ACS Nano"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e2307800120","DOI":"10.1073\/pnas.2307800120","article-title":"Endosomal escape: A bottleneck for LNP-mediated therapeutics","volume":"121","author":"Chatterjee","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Allen, R., and Yokota, T. (2024). Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids. Molecules, 29.","DOI":"10.3390\/molecules29245997"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Parvin, N., Mandal, T.K., and Joo, S.W. (2024). The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16111366"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jconrel.2024.08.030","article-title":"Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies","volume":"375","author":"Wei","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"100300","DOI":"10.1016\/j.jhepr.2021.100300","article-title":"Novel vectors and approaches for gene therapy in liver diseases","volume":"3","author":"Maestro","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"7509","DOI":"10.7150\/thno.77259","article-title":"Lipid nanoparticles for delivery of RNA therapeutics: Current status and the role of in vivo imaging","volume":"12","author":"Jung","year":"2022","journal-title":"Theranostics"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11095-022-03460-2","article-title":"Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery","volume":"40","author":"Sun","year":"2023","journal-title":"Pharm. Res."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Tseu, G.Y.W., and Kamaruzaman, K.A. (2023). A Review of Different Types of Liposomes and Their Advancements as a Form of Gene Therapy Treatment for Breast Cancer. Molecules, 28.","DOI":"10.3390\/molecules28031498"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.addr.2015.09.012","article-title":"PEGylation as a strategy for improving nanoparticle-based drug and gene delivery","volume":"99","author":"Suk","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Pandey, K., Jha, S., Chaliha, L.B., Gosai, H., and Patel, R. (2026). Nanomaterial-enabled RNA therapeutics: Bridging delivery barriers to clinical translation. Front. Nanotechnol., 8.","DOI":"10.3389\/fnano.2026.1860221"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Shevelev, A., Pozdniakova, N., Generalov, E., and Tarasova, O. (2025). siRNA Therapeutics for the Treatment of Hereditary Diseases and Other Conditions: A Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178651"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Lundstrom, K. (2020). Viral Vectors Applied for RNAi-Based Antiviral Therapy. Viruses, 12.","DOI":"10.3390\/v12090924"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/s41467-020-14527-2","article-title":"Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA","volume":"11","author":"Patel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.xphs.2022.12.026","article-title":"Effect of Cholesterol Content of Lipid Composition in mRNA-LNPs on the Protein Expression in the Injected Site and Liver After Local Administration in Mice","volume":"112","author":"Kawaguchi","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1039\/D0BM01609H","article-title":"Helper lipid structure influences protein adsorption and delivery of lipid nanoparticles to spleen and liver","volume":"9","author":"Zhang","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_142","first-page":"e67047","article-title":"Synthesizing Lipid Nanoparticles by Turbulent Flow in Confined Impinging Jet Mixers","volume":"210","author":"Subraveti","year":"2024","journal-title":"J. Vis. Exp."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e18595","DOI":"10.1002\/aic.18595","article-title":"Impinging jet mixers: A review of their mixing characteristics, performance considerations, and applications","volume":"71","author":"Devos","year":"2025","journal-title":"AIChE J."},{"key":"ref_144","first-page":"30573","article-title":"Advances in nanomaterials for precision drug delivery: Insights into pharmacokinetics and toxicity","volume":"15","author":"Tripathi","year":"2025","journal-title":"Bioimpacts"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, L., Liu, C., Luo, Y., and Chen, D. (2024). Peptide-Mediated Nanocarriers for Targeted Drug Delivery: Developments and Strategies. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16020240"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Omidian, H., Cubeddu, L.X., and Wilson, R.L. (2025). Peptide-Functionalized Nanomedicine: Advancements in Drug Delivery, Diagnostics, and Biomedical Applications. Molecules, 30.","DOI":"10.3390\/molecules30071572"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Volovat, S.R., Augustin, I.G., Volovat, C., Vasilache, I., Ostafe, M., Panaite, D.I., Burlacu, A., and Volovat, C.C. (2026). Rewriting Tumor Entry Rules: Microfluidic Polyplexes and Tumor-Penetrating Strategies\u2014A Literature Review. Pharmaceutics, 18.","DOI":"10.3390\/pharmaceutics18010084"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Ismail, A., and Chou, S.F. (2025). Polyethylenimine Carriers for Drug and Gene Delivery. Polymers, 17.","DOI":"10.3390\/polym17152150"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.jconrel.2023.09.001","article-title":"Polyethylenimine (PEI) in gene therapy: Current status and clinical applications","volume":"362","author":"Casper","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"9069","DOI":"10.1039\/D6CC01040G","article-title":"Precision-engineered polymer topologies: Balancing potent antibacterial efficacy with enhanced biocompatibility","volume":"62","author":"Aquib","year":"2026","journal-title":"Chem. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Rezvantalab, S., Drude, N.I., Moraveji, M.K., Guvener, N., Koons, E.K., Shi, Y., Lammers, T., and Kiessling, F. (2018). PLGA-Based Nanoparticles in Cancer Treatment. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01260"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Stevanovic, M.M., Qian, K., Huang, L., and Vukomanovic, M. (2025). PLGA-Based Co-Delivery Nanoformulations: Overview, Strategies, and Recent Advances. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17121613"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"152049","DOI":"10.1016\/j.bbrc.2025.152049","article-title":"Folic acid-functionalized PLGA nanomedicines encapsulating echinacoside for liver cancer therapy","volume":"774","author":"Han","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_154","first-page":"30269","article-title":"Advances in nanocarrier-mediated delivery of chrysin: Enhancing solubility, bioavailability, and anticancer efficacy","volume":"15","author":"Dabiri","year":"2025","journal-title":"Bioimpacts"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.2147\/IJN.S490444","article-title":"How Advanced are Self-Assembled Nanomaterials for Targeted Drug Delivery? A Comprehensive Review of the Literature","volume":"20","author":"Nsairat","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1021\/acs.molpharmaceut.3c00231","article-title":"Lipoic Acid-Based Poly(disulfide)s as Versatile Biomolecule Delivery Vectors and the Application in Tumor Immunotherapy","volume":"20","author":"Hei","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Dzmitruk, V., Apartsin, E., Ihnatsyeu-Kachan, A., Abashkin, V., Shcharbin, D., and Bryszewska, M. (2018). Dendrimers Show Promise for siRNA and microRNA Therapeutics. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030126"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3726","DOI":"10.1021\/acsbiomaterials.5c00336","article-title":"Changes in Generations of PAMAM Dendrimers and Compositions of Nucleic Acid Nanoparticles Govern Delivery and Immune Recognition","volume":"11","author":"Avila","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1021\/cr500542t","article-title":"Surface-engineered dendrimers in gene delivery","volume":"115","author":"Yang","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.actbio.2016.07.015","article-title":"PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery","volume":"43","author":"Luong","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Moreno-Vargas, L.M., and Prada-Gracia, D. (2024). Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010059"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e202300236","DOI":"10.1002\/cmdc.202300236","article-title":"Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications","volume":"18","author":"Gori","year":"2023","journal-title":"ChemMedChem"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1039\/D0CB00114G","article-title":"Activatable cell-penetrating peptides: 15 years of research","volume":"1","author":"Bonger","year":"2020","journal-title":"RSC Chem. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/acs.bioconjchem.5b00066","article-title":"Enzyme-Activatable Cell-Penetrating Peptides through a Minimal Side Chain Modification","volume":"26","author":"Bode","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/nat.2018.0736","article-title":"GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics","volume":"28","author":"Springer","year":"2018","journal-title":"Nucleic Acid. Ther."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"109426","DOI":"10.1016\/j.carres.2025.109426","article-title":"Advancement of drugs conjugated with GalNAc in the targeted delivery to hepatocytes based on asialoglycoprotein receptor","volume":"552","author":"Zhang","year":"2025","journal-title":"Carbohydr. Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/17425247.2025.2466767","article-title":"GalNac-siRNA conjugate delivery technology promotes the treatment of typical chronic liver diseases","volume":"22","author":"Qin","year":"2025","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.jconrel.2025.01.060","article-title":"Receptor-ligand interactions for optimized endocytosis in targeted therapies","volume":"380","author":"Sung","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1007\/s13346-023-01361-4","article-title":"Innate immune regulations and various siRNA modalities","volume":"13","author":"Kaushal","year":"2023","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"107292","DOI":"10.1016\/j.ejps.2025.107292","article-title":"Advances in the pharmaceutical development of antibody-oligonucleotide conjugates","volume":"215","author":"Li","year":"2025","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"5881","DOI":"10.1038\/s41598-021-85352-w","article-title":"Non-specific interactions of antibody-oligonucleotide conjugates with living cells","volume":"11","author":"Lehot","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Dugal-Tessier, J., Thirumalairajan, S., and Jain, N. (2021). Antibody-Oligonucleotide Conjugates: A Twist to Antibody-Drug Conjugates. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040838"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1093\/nar\/gkad415","article-title":"Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs)","volume":"51","author":"Malecova","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Taghdiri, M., and Mussolino, C. (2024). Viral and Non-Viral Systems to Deliver Gene Therapeutics to Clinical Targets. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137333"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40259-017-0234-5","article-title":"Adeno-Associated Virus (AAV) as a Vector for Gene Therapy","volume":"31","author":"Naso","year":"2017","journal-title":"BioDrugs"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Wahane, A., Waghmode, A., Kapphahn, A., Dhuri, K., Gupta, A., and Bahal, R. (2020). Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy. Molecules, 25.","DOI":"10.3390\/molecules25122866"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2614125","DOI":"10.1080\/10717544.2026.2614125","article-title":"Non-Viral CRISPR carriers: Transient delivery with lasting effects","volume":"33","author":"Lummerstorfer","year":"2026","journal-title":"Drug Deliv."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","article-title":"Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing","volume":"15","author":"Cheng","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Bhujel, R., Enkmann, V., Burgstaller, H., and Maharjan, R. (2025). Artificial Intelligence-Driven Strategies for Targeted Delivery and Enhanced Stability of RNA-Based Lipid Nanoparticle Cancer Vaccines. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17080992"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1016\/j.apsb.2026.01.039","article-title":"Artificial intelligence in biologic drug discovery: A review of methodological evolution and therapeutic applications","volume":"16","author":"Tang","year":"2026","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1038\/s12276-023-01086-x","article-title":"Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics","volume":"55","author":"Lee","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"13039","DOI":"10.2147\/IJN.S554821","article-title":"Bridging the Gap: The Role of Advanced Formulation Strategies in the Clinical Translation of Nanoparticle-Based Drug Delivery Systems","volume":"20","author":"Herdiana","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4103\/ijcm.ijcm_544_23","article-title":"The New Era of mRNA Vaccines: The Success of the COVID-19 Vaccines and the Safety Concerns in Adolescents","volume":"50","author":"Gopal","year":"2025","journal-title":"Indian J. Community Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","article-title":"mRNA vaccines for infectious diseases: Principles, delivery and clinical translation","volume":"20","author":"Chaudhary","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Sofroniou, A., and Ridley, A. (2025). A Systematic Review of Clinical Trials Using mRNA Vaccines for Infectious Diseases other than COVID-19. Br. J. Biomed. Sci., 82.","DOI":"10.3389\/bjbs.2025.14557"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"402","DOI":"10.4140\/TCP.n.2025.402","article-title":"A Review of Respiratory Syncytial Virus Vaccines in the Older Adult","volume":"40","author":"Torres","year":"2025","journal-title":"Sr. Care Pharm."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"126847","DOI":"10.1016\/j.vaccine.2025.126847","article-title":"A phase 3 randomized safety and immunogenicity trial of mRNA-1010 seasonal influenza vaccine in adults","volume":"50","author":"Soens","year":"2025","journal-title":"Vaccine"},{"key":"ref_188","first-page":"e84529","article-title":"The Future of mRNA Vaccines: Potential Beyond COVID-19","volume":"17","author":"Saxena","year":"2025","journal-title":"Cureus"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1208\/s12249-021-02058-y","article-title":"Tozinameran (BNT162b2) Vaccine: The Journey from Preclinical Research to Clinical Trials and Authorization","volume":"22","author":"Khehra","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cytogfr.2022.10.001","article-title":"Development of mRNA vaccines against respiratory syncytial virus (RSV)","volume":"68","author":"Qiu","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"2632657","DOI":"10.1080\/14760584.2026.2632657","article-title":"Preventing COVID-19 in at-risk populations: Moving toward next-generation mRNA-1283 COVID-19 vaccine to address current challenges","volume":"25","author":"Domachowske","year":"2026","journal-title":"Expert Rev. Vaccines"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1076\/ocii.7.3.189.4007","article-title":"Fomivirsen\u2014A phosphorothioate oligonucleotide for the treatment of CMV retinitis","volume":"7","author":"Meenken","year":"1999","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1080\/14656566.2018.1550071","article-title":"Mipomersen and its use in familial hypercholesterolemia","volume":"20","author":"Parham","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s40265-016-0657-1","article-title":"Eteplirsen: First Global Approval","volume":"76","author":"Syed","year":"2016","journal-title":"Drugs"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s40265-017-0711-7","article-title":"Nusinersen: First Global Approval","volume":"77","author":"Hoy","year":"2017","journal-title":"Drugs"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1056\/NEJMoa1813279","article-title":"Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease","volume":"381","author":"Kim","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1007\/s40265-018-0968-5","article-title":"Inotersen: First Global Approval","volume":"78","author":"Keam","year":"2018","journal-title":"Drugs"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s40265-020-01267-2","article-title":"Golodirsen: First Approval","volume":"80","author":"Heo","year":"2020","journal-title":"Drugs"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s40265-020-01339-3","article-title":"Viltolarsen: First Approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s40265-021-01512-2","article-title":"Casimersen: First Approval","volume":"81","author":"Shirley","year":"2021","journal-title":"Drugs"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s40265-023-01904-6","article-title":"Tofersen: First Approval","volume":"83","author":"Blair","year":"2023","journal-title":"Drugs"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s40265-024-02008-5","article-title":"Eplontersen: First Approval","volume":"84","author":"Nie","year":"2024","journal-title":"Drugs"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s40265-024-02080-x","article-title":"Imetelstat: First Approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s40265-025-02166-0","article-title":"Olezarsen: First Approval","volume":"85","author":"Syed","year":"2025","journal-title":"Drugs"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s40265-025-02257-y","article-title":"Donidalorsen: First Approval","volume":"86","author":"Syed","year":"2026","journal-title":"Drugs"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s40265-018-0983-6","article-title":"Patisiran: First Global Approval","volume":"78","author":"Hoy","year":"2018","journal-title":"Drugs"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s40265-020-01269-0","article-title":"Givosiran: First Approval","volume":"80","author":"Scott","year":"2020","journal-title":"Drugs"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s40265-020-01463-0","article-title":"Lumasiran: First Approval","volume":"81","author":"Scott","year":"2021","journal-title":"Drugs"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s40265-021-01473-6","article-title":"Inclisiran: First Approval","volume":"81","author":"Lamb","year":"2021","journal-title":"Drugs"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s40265-022-01765-5","article-title":"Vutrisiran: First Approval","volume":"82","author":"Keam","year":"2022","journal-title":"Drugs"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s40265-023-01976-4","article-title":"Nedosiran: First Approval","volume":"83","author":"Syed","year":"2023","journal-title":"Drugs"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s40265-025-02203-y","article-title":"Fitusiran: First Approval","volume":"85","author":"Lee","year":"2025","journal-title":"Drugs"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s40265-026-02293-2","article-title":"Plozasiran: First Approval","volume":"86","author":"Syed","year":"2026","journal-title":"Drugs"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1517\/14656566.6.8.1421","article-title":"Pegaptanib: The first antiangiogenic agent approved for neovascular macular degeneration","volume":"6","author":"Doggrell","year":"2005","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1007\/s40265-023-01948-8","article-title":"Avacincaptad Pegol: First Approval","volume":"83","author":"Kang","year":"2023","journal-title":"Drugs"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s40291-024-00696-z","article-title":"Exagamglogene Autotemcel: First Approval","volume":"28","author":"Hoy","year":"2024","journal-title":"Mol. Diagn. Ther."},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Yousefpour, P., Gregory, J.R., Si, K., Lonzaric, J., Li, Y., Wang, J., Qureshi, K., Ledbetter, A., Melo, M.B., and Hostetler, A. (2026). Engineering drug-responsive replication machinery for precise control of self-amplifying RNA. Nat. Biomed. Eng., online ahead of print.","DOI":"10.1038\/s41551-026-01723-6"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"2530291","DOI":"10.1080\/21645515.2025.2530291","article-title":"A second-generation, self-amplifying COVID-19 Vaccine: World\u2019s first approval and distribution in the Japanese market with vaccine hesitancy","volume":"21","author":"Naito","year":"2025","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41431-019-0508-0","article-title":"Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database","volume":"28","author":"Lambert","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4274\/balkanmedj.galenos.2025.2025-270125","article-title":"The Importance of Genetic Diagnosis in Rare Diseases","volume":"42","author":"Gurkan","year":"2025","journal-title":"Balk. Med. J."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/mutage\/geae002","article-title":"Next-generation therapeutics for rare genetic disorders","volume":"39","author":"Sankar","year":"2024","journal-title":"Mutagenesis"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/gt.2017.59","article-title":"Spinraza-a rare disease success story","volume":"24","author":"Prakash","year":"2017","journal-title":"Gene Ther."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"108983","DOI":"10.1016\/j.clineuro.2025.108983","article-title":"Real-world data on the effect of long-term treatment with nusinersen over > 4 years in a cohort of Swiss patients with spinal muscular atrophy","volume":"255","author":"Tscherter","year":"2025","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/17460441.2026.2652440","article-title":"The impact of antisense oligonucleotide (ASO) therapeutics on the future of rare disease drug discovery","volume":"21","author":"Ruchi","year":"2026","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Rodriguez Carstens, P., Moriyama, H., and Yokota, T. (2026). From Genomic Diagnosis to Personalized RNA Medicine: Advances in Next-Generation Sequencing and N-of-1 Antisense Oligonucleotide Therapies for Rare Genetic Diseases. Genes, 17.","DOI":"10.3390\/genes17030318"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"e146090","DOI":"10.1172\/jci.insight.146090","article-title":"Antisense oligonucleotide therapy for KCNT1 encephalopathy","volume":"7","author":"Burbano","year":"2022","journal-title":"JCI Insight"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/s41586-023-06277-0","article-title":"A framework for individualized splice-switching oligonucleotide therapy","volume":"619","author":"Kim","year":"2023","journal-title":"Nature"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1038\/s41591-024-03197-y","article-title":"Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder","volume":"30","author":"Ziegler","year":"2024","journal-title":"Nat. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1001\/jamaneurol.2024.4631","article-title":"Five-Year Results with Patisiran for Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Randomized Clinical Trial with Open-Label Extension","volume":"82","author":"Adams","year":"2025","journal-title":"JAMA Neurol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5582\/ddt.2025.01031","article-title":"Fitusiran: The first approved siRNA therapy for hemophilia via reducing plasma antithrombin levels","volume":"19","author":"Lu","year":"2025","journal-title":"Drug Discov. Ther."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"5879","DOI":"10.1007\/s12325-025-03382-6","article-title":"Therapeutic Advances in Hereditary Angioedema: A Focus on Present and Future Options","volume":"42","author":"Uminski","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40035-025-00477-6","article-title":"Gene therapy breakthroughs in ALS: A beacon of hope for 20% of ALS patients","volume":"14","author":"Xie","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"102459","DOI":"10.1016\/j.xcrm.2025.102459","article-title":"Emerging trends in gene and cell therapy: CRISPR in DNA editing and beyond","volume":"7","author":"Ji","year":"2026","journal-title":"Cell Rep. Med."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Laurent, M., Geoffroy, M., Pavani, G., and Guiraud, S. (2024). CRISPR-Based Gene Therapies: From Preclinical to Clinical Treatments. Cells, 13.","DOI":"10.3390\/cells13100800"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1056\/NEJMoa2107454","article-title":"CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis","volume":"385","author":"Gillmore","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/d41573-020-00096-y","article-title":"Gene-editing pipeline takes off","volume":"19","author":"Mullard","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne muscular dystrophy","volume":"7","author":"Duan","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"gkaf1518","DOI":"10.1093\/nar\/gkaf1518","article-title":"RNA editing for the treatment of alpha-1 antitrypsin deficiency","volume":"54","author":"Monian","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.tips.2021.10.012","article-title":"CRISPR-based therapeutics: Current challenges and future applications","volume":"43","author":"Modell","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Caturano, A. (2024). Cardiovascular and Metabolic Disease: New Treatments and Future Directions 2.0. Biomedicines, 12.","DOI":"10.3390\/books978-3-7258-1668-2"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Sarzani, R., Spannella, F., Di Pentima, C., Giulietti, F., Landolfo, M., and Allevi, M. (2023). Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010328"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"e032031","DOI":"10.1161\/JAHA.123.032031","article-title":"Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story of Inclisiran","volume":"13","author":"Wilkinson","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2174\/011871529X428489260113103704","article-title":"Lowering of Lipoprotein(a) with Olpasiran","volume":"26","author":"Tweneboah","year":"2026","journal-title":"Cardiovasc. Hematol. Disord. Drug Targets"},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Morosan, P.A., Bobu, A.M., Carauleanu, A., Popa, R., Costea, C.F., Filip, C., Buzduga, C.M., Patrascanu, E., Cucu, A.I., and Tudosa, R.I. (2025). Zilebesiran as an Innovative siRNA-Based Therapeutic Approach for Hypertension: Emerging Perspectives in Cardiovascular Medicine. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110717"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/bs.pmbts.2023.12.014","article-title":"RNA therapeutics for metabolic disorders","volume":"Volume 203","author":"Vu","year":"2024","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1","DOI":"10.55730\/1300-0144.5938","article-title":"Paradigm shift in obesity treatment: An extensive review of current pipeline agents","volume":"55","author":"Cetin","year":"2025","journal-title":"Turk. J. Med. Sci."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.3350\/cmh.2024.0438","article-title":"Precision medicine and nucleotide-based therapeutics to treat steatotic liver disease","volume":"31","author":"Caddeo","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_249","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"100562","DOI":"10.1016\/j.medj.2024.11.015","article-title":"Clinical advances of mRNA vaccines for cancer immunotherapy","volume":"6","author":"Yaremenko","year":"2025","journal-title":"Med"},{"key":"ref_251","doi-asserted-by":"crossref","unstructured":"Zoroddu, S., and Bagella, L. (2025). Next-Generation mRNA Vaccines in Melanoma: Advances in Delivery and Combination Strategies. Cells, 14.","DOI":"10.3390\/cells14181476"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"20","DOI":"10.21037\/tgh-24-121","article-title":"A new dawn in cancer immunotherapy: The promise of mutant KRAS-specific vaccines","volume":"10","author":"Damle","year":"2025","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41541-026-01426-8","article-title":"The current landscape of therapeutic vaccination approaches for treatment of HPV-dependent malignancies","volume":"11","author":"Schlosser","year":"2026","journal-title":"npj Vaccines"},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Bartolucci, D., Pession, A., Hrelia, P., and Tonelli, R. (2022). Precision Anti-Cancer Medicines by Oligonucleotide Therapeutics in Clinical Research Targeting Undruggable Proteins and Non-Coding RNAs. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071453"},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Khuu, A., Verreault, M., Colin, P., Tran, H., and Idbaih, A. (2024). Clinical Applications of Antisense Oligonucleotides in Cancer: A Focus on Glioblastoma. Cells, 13.","DOI":"10.3390\/cells13221869"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"100484","DOI":"10.1016\/j.jgeb.2025.100484","article-title":"Small interfering RNA: From designing to therapeutic in cancer","volume":"23","author":"Singh","year":"2025","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"Lenk, R., Kleindienst, W., Szabo, G.T., Baiersdorfer, M., Boros, G., Keller, J.M., Mahiny, A.J., and Vlatkovic, I. (2024). Understanding the impact of in vitro transcription byproducts and contaminants. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1426129"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/s41573-025-01237-x","article-title":"RNA chemistry and therapeutics","volume":"24","author":"Wang","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1002\/cpz1.39","article-title":"Cap 1 Messenger RNA Synthesis with Co-transcriptional CleanCap((R)) Analog by In Vitro Transcription","volume":"1","author":"Henderson","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"102456","DOI":"10.1016\/j.omtn.2025.102456","article-title":"CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA","volume":"36","author":"Mandell","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jconrel.2015.08.051","article-title":"N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice","volume":"217","author":"Andries","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"114471","DOI":"10.1016\/j.jconrel.2025.114471","article-title":"A systemic evaluation of the effect of dsRNA contamination on mRNA vaccine expression and immunogenicity","volume":"389","author":"Jo","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.omtn.2019.02.018","article-title":"A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA","volume":"15","author":"Baiersdorfer","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_264","first-page":"100095","article-title":"Digitalization in pharmaceutical industry: What to focus on under the digital implementation process?","volume":"3","author":"Hole","year":"2021","journal-title":"Int. J. Pharm. X"},{"key":"ref_265","doi-asserted-by":"crossref","unstructured":"Jandang, W., Saokham, P., Prathumwon, C., Okonogi, S., and Ampasavate, C. (2026). Quality by Design-Based Scale-Up and Industrial Development of Turmeric Extract-Loaded Nanostructured Lipid Carriers. Pharmaceutics, 18.","DOI":"10.3390\/pharmaceutics18040492"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"100916","DOI":"10.1016\/j.jpha.2023.12.006","article-title":"Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics","volume":"14","author":"Limpikirati","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Pavcnik, L., Prunk, M., Trdan Lusin, T., and Roskar, R. (2025). Accelerated Predictive Stability Testing: Accelerating Registration Phase and Application of Reduced Designs for Shelf-Life Determination of Parenteral Drug Product. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17020160"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1002\/bit.70196","article-title":"Real-Time Monitoring of In Vitro Transcription for Production of mRNA Using Raman Spectroscopy","volume":"123","author":"Fulber","year":"2026","journal-title":"Biotechnol. Bioeng."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s43441-025-00752-8","article-title":"Toward an Extensible Regulatory Framework for N-of-1 to N-of-Few Personalized RNA Therapy Design","volume":"59","author":"Pereme","year":"2025","journal-title":"Ther. Innov. Regul. Sci."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s42003-026-09650-7","article-title":"Model selection in preclinical nucleic acid therapeutics research","volume":"9","author":"Oliver","year":"2026","journal-title":"Commun. Biol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"gkaf778","DOI":"10.1093\/nar\/gkaf778","article-title":"Translational and clinical development of therapeutic siRNA and ASOs: Current industry practices, perspectives, and recommendations","volume":"53","author":"Christensen","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"gkag345","DOI":"10.1093\/nar\/gkag345","article-title":"Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency","volume":"54","author":"Chickering","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"176731","DOI":"10.1016\/j.cej.2026.176731","article-title":"From selection to design: Reshaping aptamer discovery with artificial intelligence","volume":"538","author":"Yang","year":"2026","journal-title":"Chem. Eng. J."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"e27966","DOI":"10.1016\/j.heliyon.2024.e27966","article-title":"Development of quantitative structure activity relationships (QSARs) for predicting the aggregation of TiO(2) nanoparticles under favorable conditions","volume":"10","author":"Lee","year":"2024","journal-title":"Heliyon"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.apsb.2025.12.011","article-title":"Machine learning empowered formulation design, optimization and characterization of nanoparticulate drug delivery systems: Current applications, challenges, and future perspectives","volume":"16","author":"Shen","year":"2026","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_276","doi-asserted-by":"crossref","unstructured":"Tan, T., Diao, Y., Yu, X., Chen, L., and Fang, H. (Acta Pharm. Sin. B, 2026). Artificial intelligence in precision mRNA therapeutics: Towards genomic language models and multi-agent virtual humans, Acta Pharm. Sin. B, in press.","DOI":"10.1016\/j.apsb.2025.12.044"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/8\/809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:08:53Z","timestamp":1786446533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/8\/809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":276,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cimb48080809"],"URL":"https:\/\/doi.org\/10.3390\/cimb48080809","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}