{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:15:19Z","timestamp":1791918919624,"version":"4.3.4"},"reference-count":231,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In the realm of gene therapy, a pivotal moment arrived with Paul Berg\u2019s groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause\u2014the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich assortment of 16 drugs, from siRNA, miRNA, and CRISPR\/Cas9 to DNA aptamers and TRAIL\/APO2L, as well as 46 carriers, from AAV, AdV, LNPs, and exosomes to naked mRNA, sonoporation, and magnetofection. The article also discusses the advantages and disadvantages of each product and vector type, as well as the current challenges faced in the practical use of gene therapy and its future potential.<\/jats:p>","DOI":"10.3390\/ph16101416","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T03:05:19Z","timestamp":1696475119000},"page":"1416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Current State of Human Gene Therapy: Approved Products and Vectors"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2353-8552","authenticated-orcid":false,"given":"Aladdin Y.","family":"Shchaslyvyi","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Zabolotnogo Str., 03143 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana V.","family":"Antonenko","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Zabolotnogo Str., 03143 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maksym G.","family":"Tesliuk","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Zabolotnogo Str., 03143 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennadiy D.","family":"Telegeev","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Zabolotnogo Str., 03143 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/jgm.619","article-title":"Gene therapy clinical trials worldwide 1989\u20132004\u2014An overview","volume":"6","author":"Edelstein","year":"2004","journal-title":"J. Gene Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arabi, F., Mansouri, V., and Ahmadbeigi, N. (2022). Gene therapy clinical trials, where do we go? An overview. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113324"},{"key":"ref_3","first-page":"104","article-title":"Discovery of DNA as the hereditary material using Streptococcus pneumoniae","volume":"1","year":"2008","journal-title":"Nat. Educ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1177\/0022034509337480","article-title":"Gene therapy: Design and prospects for craniofacial regeneration","volume":"88","author":"Scheller","year":"2009","journal-title":"J. Dent. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1126\/science.adh2943","article-title":"Paul Berg (1926\u20132023)","volume":"379","author":"Baltimore","year":"2023","journal-title":"Science"},{"key":"ref_6","unstructured":"(2023, July 04). Approval Letter\u2014KYMRIAH, Available online: https:\/\/www.fda.gov\/media\/106989\/download."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"868","DOI":"10.3389\/fgene.2019.00868","article-title":"Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders","volume":"10","author":"Shahryari","year":"2019","journal-title":"Front. Genet."},{"key":"ref_8","first-page":"447","article-title":"Parsing clinical success rates","volume":"15","author":"Mullard","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"48","DOI":"10.59566\/IJBS.2017.13048","article-title":"Molecular mechanisms and biological functions of siRNA","volume":"13","author":"Dana","year":"2017","journal-title":"Int. J. Biomed. Sci."},{"key":"ref_10","first-page":"560","article-title":"RNA Interference Technology","volume":"5","author":"Xu","year":"2019","journal-title":"Compr. Biotechnol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/nrn2205","article-title":"siRNA: Brain delivery breakthrough","volume":"8","author":"Flemming","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrd3010","article-title":"Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application","volume":"9","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/oli.2009.0180","article-title":"siRNA and innate immunity","volume":"19","author":"Robbins","year":"2009","journal-title":"Oligonucleotides"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrm3838","article-title":"Regulation of microRNA biogenesis","volume":"15","author":"Ha","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brennecke, J., Stark, A., Russell, R.B., and Cohen, S.M. (2005). Principles of MicroRNA\u2013Target Recognition. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030085"},{"key":"ref_17","first-page":"432","article-title":"piRNAs: Nature, biogenesis, regulation, and their potential clinical utility","volume":"78","year":"2021","journal-title":"Bol. Med. Hosp. Infant. Mex."},{"key":"ref_18","first-page":"141","article-title":"Short Hairpin RNA (shRNA): Design, Delivery, and Assessment of Gene Knockdown","volume":"629","author":"Moore","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1261\/rna.1894510","article-title":"Minimal-length short hairpin RNAs: The relationship of structure and RNAi activity","volume":"16","author":"Ge","year":"2010","journal-title":"RNA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Larsson, E., Sander, C., and Marks, D. (2010). mRNA turnover rate limits siRNA and microRNA efficacy. Mol. Syst. Biol., 6.","DOI":"10.1038\/msb.2010.89"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/ncb2895","article-title":"Stable RNA interference rules for silencing","volume":"16","author":"Fellmann","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mcintyre, G.J., Yu, Y.-H., Lomas, M., and Fanning, G.C. (2011). The effects of stem length and core placement on shRNA activity. BMC Mol. Biol., 12.","DOI":"10.1186\/1471-2199-12-34"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dhuri, K., Bechtold, C., Quijano, E., Pham, H., Gupta, A., Vikram, A., and Bahal, R. (2020). Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development. J. Clin. Med., 9.","DOI":"10.3390\/jcm9062004"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e323","DOI":"10.1212\/NXG.0000000000000323","article-title":"Antisense oligonucleotides","volume":"5","author":"Scoles","year":"2019","journal-title":"Neurol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"McClorey, G., and Banerjee, S. (2018). Cell-Penetrating Peptides to Enhance Delivery of Oligonucleotide-Based Therapeutics. Biomedicines, 6.","DOI":"10.3390\/biomedicines6020051"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/j.ymthe.2017.06.002","article-title":"RNase H1-Dependent Antisense Oligonucleotides Are Robustly Active in Directing RNA Cleavage in Both the Cytoplasm and the Nucleus","volume":"25","author":"Liang","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/gtc.12730","article-title":"Evaluation of off-target effects of gapmer antisense oligonucleotides using human cells","volume":"24","author":"Yoshida","year":"2019","journal-title":"Genes Cells"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s40259-022-00519-9","article-title":"Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic","volume":"36","author":"Rook","year":"2022","journal-title":"BioDrugs"},{"key":"ref_30","first-page":"RA110","article-title":"Vectors and delivery systems in gene therapy","volume":"11","author":"Hodosy","year":"2005","journal-title":"Med. Sci. Monit."},{"key":"ref_31","first-page":"353","article-title":"Mechanism and Applications of CRISPR\/Cas-9-Mediated Genome Editing","volume":"15","author":"Asmamaw","year":"2021","journal-title":"Biologics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xu, C.L., Ruan, M.Z.C., Mahajan, V.B., and Tsang, S.H. (2019). Viral Delivery Systems for CRISPR. Viruses, 11.","DOI":"10.3390\/v11010028"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Naeem, M., Majeed, S., Hoque, M.Z., and Ahmad, I. (2020). Latest Developed Strategies to Minimize the Off-Target Effects in CRISPR-Cas-Mediated Genome Editing. Cells, 9.","DOI":"10.3390\/cells9071608"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rawashdeh, O., Rawashdeh, R.Y., Kebede, T., Kapp, D., and Ralescu, A. (2022). Bio-informatic analysis of CRISPR protospacer adjacent motifs (PAMs) in T4 genome. BMC Genom. Data, 23.","DOI":"10.1186\/s12863-022-01056-8"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"649896","DOI":"10.3389\/fmed.2021.649896","article-title":"CRISPR\/Cas: Advances, Limitations, and Applications for Precision Cancer Research","volume":"8","author":"Yang","year":"2021","journal-title":"Front. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.2174\/156802612803531342","article-title":"Therapeutic option of plasmid-DNA based gene transfer","volume":"12","author":"Taniyama","year":"2012","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5661\/bger-26-83","article-title":"Biomedical application of plasmid DNA in gene therapy: A new challenge for chromatography","volume":"26","author":"Sousa","year":"2009","journal-title":"Biotechnol. Genet. Eng. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1155\/S1110724303209086","article-title":"Gene Therapy for Cardiovascular Disease","volume":"2","author":"Dishart","year":"2003","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1038\/s41467-022-30355-y","article-title":"PlasmidMaker is a versatile, automated, and high throughput end-to-end platform for plasmid construction","volume":"13","author":"Enghiad","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Shintani, M., Sanchez, Z.K., and Kimbara, K. (2015). Genomics of microbial plasmids: Classification and identification based on replication and transfer systems and host taxonomy. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00242"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1089\/hum.1998.9.17-2545","article-title":"Enhancer and promoter chimeras in plasmids designed for intramuscular injection: A comparative in vivo and in vitro study","volume":"9","author":"Barnhart","year":"1998","journal-title":"Hum. Gene Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1016\/j.drudis.2021.06.008","article-title":"Methods to improve the immunogenicity of plasmid DNA vaccines","volume":"26","author":"Neves","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_43","first-page":"352","article-title":"Colocalization of USP1 and \u0420\u041d domain of Bcr-Abl oncoprotein in terms of chronic myeloid leukemia cell rearrangements","volume":"50","author":"Antonenko","year":"2016","journal-title":"Tsitol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.32471\/exp-oncology.2312-8852.vol-42-no-2.14533","article-title":"Inhibition of USP1, a new partner of bcr-abl, results in decrease of Bcr-Abl level in k562 cells","volume":"42","author":"Antonenko","year":"2020","journal-title":"Exp. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3103\/S0095452720010028","article-title":"GLG1 in K562 cells: Role in pathogenesis of chronic myeloid leukemia","volume":"54","author":"Antonenko","year":"2020","journal-title":"Cytol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.3389\/fonc.2019.01208","article-title":"Therapeutic Prospects of mRNA-Based Gene Therapy for Glioblastoma","volume":"9","author":"Tang","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2015.12.008","article-title":"Pros and cons of pDNA and mRNA transfection to study mRNA translation in mammalian cells","volume":"578","author":"Andreev","year":"2016","journal-title":"Gene"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Damase, T.R., Sukhovershin, R., Boada, C., Taraballi, F., Pettigrew, R.I., and Cooke, J.P. (2021). The Limitless Future of RNA Therapeutics. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.628137"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Iqbal, Z., Iqbal, M.S., Ahmad, A., Memon, A.G., and Ansari, M.I. (2020). New prospects on the horizon: Genome editing to engineer plants for desirable traits. Curr. Plant Biol., 24.","DOI":"10.1016\/j.cpb.2020.100171"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pinkert, C.A. (2014). Transgenic Animal Technology, Elsevier. [3rd ed.].","DOI":"10.1016\/B978-0-12-410490-7.00001-3"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/156652311794520111","article-title":"Meganucleases and Other Tools for Targeted Genome Engineering: Perspectives and Challenges for Gene Therapy","volume":"11","author":"Silva","year":"2011","journal-title":"Curr. Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhang, F., Puchta, H., and Thomson, J. (2015). Advances in New Technology for Targeted Modification of Plant Genomes, Springer.","DOI":"10.1007\/978-1-4939-2556-8"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1093\/nar\/gkg375","article-title":"A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells","volume":"31","author":"Epinat","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nrg2842","article-title":"Genome editing with engineered zinc finger nucleases","volume":"11","author":"Urnov","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5978","DOI":"10.1093\/nar\/gki912","article-title":"Zinc finger nucleases: Custom-designed molecular scissors for genome engineering of plant and mammalian cells","volume":"33","author":"Durai","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nmeth.2420","article-title":"A genome-wide TALEN resource","volume":"10","author":"Kim","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1093\/nar\/gkt789","article-title":"E-TALEN: A web tool to design TALENs for genome engineering","volume":"41","author":"Heigwer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1021\/acssynbio.5b00074","article-title":"TALENs-Assisted Multiplex Editing for Accelerated Genome Evolution To Improve Yeast Phenotypes","volume":"4","author":"Zhang","year":"2015","journal-title":"ACS Synth. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wang, L., Li, F., Dang, L., Liang, C., Wang, C., He, B., Liu, J., Li, D., Wu, X., and Xu, X. (2016). In Vivo Delivery Systems for Therapeutic Genome Editing. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050626"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14050","DOI":"10.1038\/mtm.2014.50","article-title":"Genetic rearrangements of variable di-residue (RVD)-containing repeat arrays in a baculoviral TALEN system","volume":"1","author":"Lau","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Adachi, T., and Nakamura, Y. (2019). Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application. Molecules, 24.","DOI":"10.3390\/molecules24234229"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"eabo0902","DOI":"10.1126\/sciadv.abo0902","article-title":"Efficient delivery of a DNA aptamer-based biosensor into plant cells for glucose sensing through thiol-mediated uptake","volume":"8","author":"Mou","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"423","DOI":"10.4062\/biomolther.2013.085","article-title":"Nucleic Acid Aptamers: New Methods for Selection, Stabilization, and Application in Biomedical Science","volume":"21","author":"Kong","year":"2013","journal-title":"Biomol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"20979","DOI":"10.3390\/molecules201219739","article-title":"DNA Aptamers in the Diagnosis and Treatment of Human Diseases","volume":"20","author":"Zhu","year":"2015","journal-title":"Molecules"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bios.2016.04.091","article-title":"Aptamers, antibody scFv, and antibody Fab\u2019 fragments: An overview and comparison of three of the most versatile biosensor biorecognition elements","volume":"85","author":"Thompson","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Miranda-Castro, R., de-los-Santos-\u00c1lvarez, N., Miranda-Ordieres, A.J., and Lobo-Casta\u00f1\u00f3n, M.J. (2016). Harnessing Aptamers to Overcome Challenges in Gluten Detection. Biosensors, 6.","DOI":"10.3390\/bios6020016"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8474","DOI":"10.1021\/ja2026085","article-title":"Rapid detection of a cocaine-binding aptamer using biological nanopores on a chip","volume":"133","author":"Kawano","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Xie, M., Chen, Z., Zhao, F., Lin, Y., Zheng, S., and Han, S. (2022). Selection and Application of ssDNA Aptamers for Fluorescence Biosensing Detection of Malachite Green. Foods, 11.","DOI":"10.3390\/foods11060801"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bpc.2010.09.009","article-title":"Defining the secondary structural requirements of a cocaine-binding aptamer by a thermodynamic and mutation study","volume":"153","author":"Neves","year":"2010","journal-title":"Biophys. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/jmbi.2000.3951","article-title":"2.8 \u00c5 crystal structure of the malachite green aptamer","volume":"301","author":"Baugh","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/s41401-019-0287-8","article-title":"TRAIL-based gene delivery and therapeutic strategies","volume":"40","author":"Zhong","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2174\/156652309787354612","article-title":"TRAIL gene therapy: From preclinical development to clinical application","volume":"9","author":"Griffith","year":"2009","journal-title":"Curr. Gene Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1128\/AAC.49.1.249-255.2005","article-title":"Antisense phosphorodiamidate morpholino oligomer length and target position effects on gene-specific inhibition in Escherichia coli","volume":"49","author":"Deere","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Nan, Y., and Zhang, Y.-J. (2018). Antisense phosphorodiamidate morpholino oligomers as novel antiviral compounds. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00750"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Nayerossadat, N., Maedeh, T., and Ali, P.A. (2012). Viral and nonviral delivery systems for gene delivery. Adv. Biomed. Res., 1.","DOI":"10.4103\/2277-9175.98152"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Esposito, M.V., Aveta, A., Comegna, M., Cernera, G., Iacotucci, P., Carnovale, V., Taccetti, G., Terlizzi, V., and Castaldo, G. (2020). Extensive CFTR Gene Analysis Revealed a Higher Occurrence of Cystic Fibrosis Transmembrane Regulator-Related Disorders (CFTR-RD) among CF Carriers. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123853"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/BJ20110672","article-title":"MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene","volume":"438","author":"Gillen","year":"2011","journal-title":"Biochem. J."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"De Palma, F.D.E., Raia, V., Kroemer, G., and Maiuri, M.C. (2020). The Multifaceted Roles of MicroRNAs in Cystic Fibrosis. Diagnostics, 10.","DOI":"10.3390\/diagnostics10121102"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1186\/s12967-016-1047-x","article-title":"Retroviral vectors and transposons for stable gene therapy: Advances, current challenges and perspectives","volume":"14","author":"Vargas","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/1535676019899502","article-title":"Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges","volume":"25","author":"Ghosh","year":"2020","journal-title":"Appl. Biosaf."},{"key":"ref_81","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_82","first-page":"94","article-title":"Herpesvirus Vectors in Gene Therapy","volume":"4","author":"Hukkanen","year":"2010","journal-title":"Open Virol. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.3390\/v7052321","article-title":"Alphaviruses in Gene Therapy","volume":"7","author":"Lundstrom","year":"2015","journal-title":"Viruses"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41579-022-00825-7","article-title":"A molecular understanding of alphavirus entry and antibody protection","volume":"21","author":"Kim","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/978-1-4939-9065-8_11","article-title":"Poxviruses as Gene Therapy Vectors: Generating Poxviral Vectors Expressing Therapeutic Transgenes","volume":"1937","author":"Conrad","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1038\/sj.gt.3301287","article-title":"Poxvirus as a vector to transduce human dendritic cells for immunotherapy: Abortive infection but reduced APC function","volume":"7","author":"Jenne","year":"2000","journal-title":"Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Oliveira, G.P., Rodrigues, R.A.L., Lima, M.T., Drumond, B.P., and Abrah\u00e3o, J.S. (2017). Poxvirus Host Range Genes and Virus\u2013Host Spectrum: A Critical Review. Viruses, 9.","DOI":"10.3390\/v9110331"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"109364","DOI":"10.1016\/j.intimp.2022.109364","article-title":"Poxviruses and the immune system: Implications for monkeypox virus","volume":"113","author":"Saghazadeh","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Gibb, B., Hyman, P., and Schneider, C.L. (2021). The Many Applications of Engineered Bacteriophages\u2014An Overview. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070634"},{"key":"ref_90","unstructured":"Kasman, L.M., and Porter, L.D. (2023). StatPearls [Internet], StatPearls Publishing."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0022-2836(82)90546-0","article-title":"Nucleotide sequence of bacteriophage \u03bb DNA","volume":"162","author":"Sanger","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0022-2836(83)80282-4","article-title":"Complete nucleotide sequence of bacteriophage T7 DNA and the locations of T7 genetic elements","volume":"166","author":"Dunn","year":"1983","journal-title":"J. Mol. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/1743-422X-7-292","article-title":"Genomes of the T4-related bacteriophages as windows on microbial genome evolution","volume":"7","author":"Petrov","year":"2010","journal-title":"Virol. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.mib.2008.09.004","article-title":"Bacteriophage genomics","volume":"11","author":"Hatfull","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3389\/fphar.2019.00513","article-title":"Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections","volume":"10","author":"Principi","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_96","unstructured":"Mahy, B.W.J., and van Regenmortel, M.H.V. (2008). Encyclopedia of Virology, Academic Press. [3rd ed.]."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7298","DOI":"10.1128\/jvi.67.12.7298-7306.1993","article-title":"Epstein-Barr virus recombinants from overlapping cosmid fragments","volume":"67","author":"Tomkinson","year":"1993","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Zhang, N., Zuo, Y., Jiang, L., Peng, Y., Huang, X., and Zuo, L. (2021). Epstein-Barr Virus and Neurological Diseases. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.816098"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e01390-20","DOI":"10.1128\/JVI.01390-20","article-title":"Epstein-Barr Virus Episome Physically Interacts with Active Regions of the Host Genome in Lymphoblastoid Cells","volume":"94","author":"Wang","year":"2020","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10923","DOI":"10.1128\/JVI.79.17.10923-10930.2005","article-title":"Mutations of Epstein-Barr Virus gH That Are Differentially Able To Support Fusion with B Cells or Epithelial Cells","volume":"79","author":"Wu","year":"2005","journal-title":"J. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5159","DOI":"10.2147\/IJN.S203330","article-title":"Synthesis and characterization of nanometer-sized liposomes for encapsulation and microRNA transfer to breast cancer cells","volume":"14","author":"Lujan","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jconrel.2020.04.003","article-title":"Self-assembly of amphiphilic phospholipid peptide dendrimer-based nanovectors for effective delivery of siRNA therapeutics in prostate cancer therapy","volume":"322","author":"Dong","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jcis.2023.03.043","article-title":"Facile generation of surface diversity in gold nanoparticles","volume":"641","author":"Paz","year":"2023","journal-title":"J. Colloid Interface Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1039\/D0NA00961J","article-title":"Gold nanomaterials for optical biosensing and bioimaging","volume":"3","author":"Si","year":"2021","journal-title":"Nanoscale Adv."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s12272-013-0273-5","article-title":"Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications","volume":"37","author":"Jeong","year":"2014","journal-title":"Arch. Pharm. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1021\/bc900135d","article-title":"Synthesis and Bioconjugation of 2 and 3 nm-diameter Gold Nanoparticles","volume":"21","author":"Ackerson","year":"2010","journal-title":"Bioconjug. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"101560","DOI":"10.1016\/j.jksus.2021.101560","article-title":"Gold nanoparticles: Synthesis properties and applications","volume":"33","author":"Hammami","year":"2021","journal-title":"J. King Saud Univ.-Sci."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sani, A., Cao, C., and Cui, D. (2021). Toxicity of gold nanoparticles (AuNPs): A review. Biochem. Biophys. Rep., 26.","DOI":"10.1016\/j.bbrep.2021.100991"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1039\/C5BM00629E","article-title":"Targeted delivery of microRNA-126 to vascular endothelial cells via REDV peptide modified PEG-trimethyl chitosan","volume":"4","author":"Zhou","year":"2016","journal-title":"Biomater. Sci."},{"key":"ref_110","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_111","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1021\/acs.bioconjchem.8b00749","article-title":"Enhancing the In Vitro and In Vivo Stabilities of Polymeric Nucleic Acid Delivery Nanosystems","volume":"30","author":"Wang","year":"2019","journal-title":"Bioconjug. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"31915","DOI":"10.1021\/acsami.8b09642","article-title":"Versatile Redox-Responsive Polyplexes for the Delivery of Plasmid DNA, Messenger RNA, and CRISPR-Cas9 Genome-Editing Machinery","volume":"10","author":"Wang","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_113","first-page":"19","article-title":"An overview on synthesis, properties and applications of poly(butylene-adipate-co-terephthalate)\u2013PBAT","volume":"3","author":"Jian","year":"2020","journal-title":"Adv. Ind. Eng. Polym. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.polymertesting.2013.05.001","article-title":"Biodegradation behavior of poly(butylene adipate-co-terephthalate) (PBAT), poly(lactic acid) (PLA), and their blend under soil conditions","volume":"32","author":"Weng","year":"2013","journal-title":"Polym. Test."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Phothisarattana, D., Wongphan, P., Promhuad, K., Promsorn, J., and Harnkarnsujarit, N. (2021). Biodegradable Poly(Butylene Adipate-Co-Terephthalate) and Thermoplastic Starch-Blended TiO2 Nanocomposite Blown Films as Functional Active Packaging of Fresh Fruit. Polymers, 13.","DOI":"10.3390\/polym13234192"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.clay.2013.04.015","article-title":"Characterization, degradation and biocompatibility of PBAT based nanocomposites","volume":"80\u201381","author":"Fukushima","year":"2013","journal-title":"Appl. Clay Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"18515","DOI":"10.1021\/acsami.8b03496","article-title":"A Universal GSH-Responsive Nanoplatform for the Delivery of DNA, mRNA, and Cas9\/sgRNA Ribonucleoprotein","volume":"10","author":"Chen","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"629054","DOI":"10.3389\/fchem.2021.629054","article-title":"Review on Recent Progress in Magnetic Nanoparticles: Synthesis, Characterization, and Diverse Applications","volume":"9","author":"Ali","year":"2021","journal-title":"Front. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.vetmic.2019.01.009","article-title":"Improved DNA extraction and purification with magnetic nanoparticles for the detection of methicillin-resistant Staphylococcus aureus","volume":"230","author":"Ernst","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_120","unstructured":"Chung, E.J., Leon, L., and Rinaldi, C. (2020). Nanoparticles for Biomedical Applications, Elsevier."},{"key":"ref_121","unstructured":"Ehrmann, A., Nguyen, T.A., Ahmadi, M., Farmani, A., and Nguyen-Tri, P. (2021). Magnetic Nanoparticle-Based Hybrid Materials, Woodhead Publishing."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1016\/j.synthmet.2011.05.030","article-title":"Structural and magnetic properties of iron, cobalt and nickel nanoparticles","volume":"161","author":"Alagiri","year":"2011","journal-title":"Synth. Met."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"614094","DOI":"10.1155\/2012\/614094","article-title":"Biocompatibility and Toxicity of Magnetic Nanoparticles in Regenerative Medicine","volume":"2012","author":"Markides","year":"2012","journal-title":"J. Nanomater."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.3390\/nano5042231","article-title":"Magnetic Nanoparticles Cross the Blood-Brain Barrier: When Physics Rises to a Challenge","volume":"5","author":"Busquets","year":"2015","journal-title":"Nanomaterials"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"111682","DOI":"10.1016\/j.msec.2020.111682","article-title":"Ethylcellulose nanoparticles prepared from nano-emulsion templates as new folate binding haemocompatible platforms","volume":"120","author":"Leitner","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejps.2010.03.019","article-title":"Gene delivery by lipoplexes and polyplexes","volume":"40","author":"Sun","year":"2010","journal-title":"Eur J Pharm Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jconrel.2006.06.024","article-title":"Cationic lipids, lipoplexes and intracellular delivery of genes","volume":"116","author":"Wasungu","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_128","unstructured":"Kim, N.J., Yoo, J.J., Atala, A., and Lee, S.J. (2016). Situ Tissue Regeneration, Academic Press."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Vasile, C. (2019). Polymeric Nanomaterials in Nanotherapeutics, Elsevier.","DOI":"10.1016\/B978-0-12-813932-5.00001-7"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jconrel.2020.04.041","article-title":"Micelleplexes as nucleic acid delivery systems for cancer-targeted therapies","volume":"323","author":"Jarak","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1021\/acs.biomac.2c00338","article-title":"Polycation Architecture Affects Complexation and Delivery of Short Antisense Oligonucleotides: Micelleplexes Outperform Polyplexes","volume":"23","author":"Grimme","year":"2022","journal-title":"Biomacromolecules"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.2147\/IJN.S299448","article-title":"Carbon Nanotubes: Smart Drug\/Gene Delivery Carriers","volume":"16","author":"Zare","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"724","DOI":"10.2174\/1389450117666160709023425","article-title":"Graphene: A Comprehensive Review","volume":"18","author":"Ghuge","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_134","first-page":"1515","article-title":"Functionalization and optimization-strategy of graphene oxide-based nanomaterials for gene and drug delivery","volume":"12","author":"Han","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"798440","DOI":"10.3389\/fmats.2021.798440","article-title":"Quantum Dots: An Emerging Approach for Cancer Therapy","volume":"8","author":"Devi","year":"2022","journal-title":"Front. Mater."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Singh, S., Dhawan, A., Karhana, S., Bhat, M., and Dinda, A.K. (2020). Quantum Dots: An Emerging Tool for Point-of-Care Testing. Micromachines, 11.","DOI":"10.3390\/mi11121058"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/acsmaterialslett.0c00550","article-title":"Graphene Quantum Dots (GQDs) for Bioimaging and Drug Delivery Applications: A Review","volume":"3","author":"Biswas","year":"2021","journal-title":"ACS Mater. Lett."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"23861","DOI":"10.1039\/D0RA03938A","article-title":"Graphene quantum dot based materials for sensing, bio-imaging and energy storage applications: A review","volume":"10","author":"Kumar","year":"2020","journal-title":"RSC Adv."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Henna, T.K., and Pramod, K. (2020). Graphene quantum dots redefine nanobiomedicine. Mater. Sci. Eng. C Mater. Biol. Appl., 110.","DOI":"10.1016\/j.msec.2020.110651"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.mtchem.2018.09.007","article-title":"Graphene quantum dots from chemistry to applications","volume":"10","author":"Tian","year":"2018","journal-title":"Mater. Today Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9552","DOI":"10.1038\/s41598-017-09890-y","article-title":"Simultaneous Gene Delivery and Tracking through Preparation of Photo-Luminescent Nanoparticles Based on Graphene Quantum Dots and Chimeric Peptides","volume":"7","author":"Ghafary","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"12028","DOI":"10.1038\/s41598-019-48567-6","article-title":"The Low Toxicity of Graphene Quantum Dots is Reflected by Marginal Gene Expression Changes of Primary Human Hematopoietic Stem Cells","volume":"9","author":"Fasbender","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"35472","DOI":"10.1039\/D1RA05638G","article-title":"Recent advances in functionalized upconversion nanoparticles for light-activated tumor therapy","volume":"11","author":"Chu","year":"2021","journal-title":"RSC Adv."},{"key":"ref_144","unstructured":"Chauhan, A., and Kulhari, H. (2020). Pharmaceutical Applications of Dendrimers, Elsevier."},{"key":"ref_145","unstructured":"Pednekar, P.P., Godiyal, S.C., Jadhav, K.R., and Kadam, V.J. (2017). Nanostructures for Cancer Therapy, Elsevier."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Watermann, A., and Brieger, J. (2017). Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer. Nanomaterials, 7.","DOI":"10.3390\/nano7070189"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"101350","DOI":"10.1016\/j.isci.2020.101350","article-title":"Bright Ferritin\u2014A Reporter Gene Platform for On-Demand, Longitudinal Cell Tracking on MRI","volume":"23","author":"Szulc","year":"2020","journal-title":"iScience"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Tariq, H., Batool, S., Asif, S., Ali, M., and Abbasi, B.H. (2021). Virus-Like Particles: Revolutionary Platforms for Developing Vaccines Against Emerging Infectious Diseases. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.790121"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/B978-0-12-802302-0.00003-0","article-title":"Virus-Like Particle and Nanoparticle Vaccines","volume":"13","author":"Kanekiyo","year":"2017","journal-title":"Hum. Vaccines"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jconrel.2018.02.042","article-title":"Ferritin-based drug delivery systems: Hybrid nanocarriers for vascular immunotargeting","volume":"282","author":"Khoshnejad","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.apsb.2019.01.011","article-title":"Red blood cell membrane-camouflaged nanoparticles: A novel drug delivery system for antitumor application","volume":"9","author":"Xia","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"12029","DOI":"10.1002\/anie.201506030","article-title":"Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome editing","volume":"54","author":"Sun","year":"2015","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1039\/D1BM01658J","article-title":"Non-viral delivery of the CRISPR\/Cas system: DNA versus RNA versus RNP","volume":"10","author":"Lin","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_154","first-page":"104","article-title":"Recent Progress on Nonviral Delivery Carriers for CRISPR\/Cas9 Systems","volume":"15","author":"Wang","year":"2020","journal-title":"Mater. Matters"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/s41467-018-03390-x","article-title":"ARMMs as a versatile platform for intracellular delivery of macromolecules","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_156","unstructured":"(2023, July 04). ARRDC1-Mediated Microvesicles (ARMMs) and Uses Thereof. Available online: https:\/\/patents.google.com\/patent\/US9737480B2\/en."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Tarvirdipour, S., Huang, X., Mihali, V., Schoenenberger, C.-A., and Palivan, C.G. (2020). Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application. Molecules, 25.","DOI":"10.3390\/molecules25153482"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/bip.20989","article-title":"Cell penetrating peptide-modified pharmaceutical nanocarriers for intracellular drug and gene delivery","volume":"90","author":"Torchilin","year":"2008","journal-title":"Biopolymers"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Taylor, R.E., and Zahid, M. (2020). Cell Penetrating Peptides, Novel Vectors for Gene Therapy. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030225"},{"key":"ref_160","first-page":"75","article-title":"A comprehensive overview of exosomes as drug delivery vehicles\u2014Endogenous nanocarriers for targeted cancer therapy","volume":"1846","author":"Johnsen","year":"2014","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fphar.2016.00137","article-title":"Microneedles as a delivery system for gene therapy","volume":"7","author":"Chen","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, J.A., and Lummis, S.C.R. (2011). Nano-biolistics: A method of biolistic transfection of cells and tissues using a gene gun with novel nanometer-sized projectiles. BMC Biotechnol., 11.","DOI":"10.1186\/1472-6750-11-66"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/sj.gt.3301350","article-title":"Nonviral in vivo gene delivery into tumors using a novel low volume jet-injection technology","volume":"8","author":"Walther","year":"2001","journal-title":"Gene Ther."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1046\/j.1365-201X.2003.01093.x","article-title":"Electroporation: Theory and methods, perspectives for drug delivery, gene therapy and research","volume":"177","author":"Gehl","year":"2003","journal-title":"Acta. Physiol. Scand."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/bs.adgen.2014.10.003","article-title":"Electroporation-mediated gene delivery","volume":"89","author":"Young","year":"2015","journal-title":"Adv. Genet."},{"key":"ref_166","unstructured":"(2023, July 04). Package Insert\u2014Kymriah, Available online: https:\/\/www.fda.gov\/media\/107296\/download."},{"key":"ref_167","unstructured":"Lattime, E.C., and Gerson, S.L. (2014). Gene Therapy of Cancer, Academic Press. [3rd ed.]."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Krut, Z., Gazit, D., Gazit, Z., and Pelled, G. (2022). Applications of Ultrasound-Mediated Gene Delivery in Regenerative Medicine. Bioengineering, 9.","DOI":"10.3390\/bioengineering9050190"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41596-019-0125-y","article-title":"Nonviral ultrasound-mediated gene delivery in small and large animal models","volume":"14","author":"Bez","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Chen, X., and Wong, S. (2014). Cancer Theranostics, Academic Press. [1st ed.].","DOI":"10.1016\/B978-0-12-407722-5.00001-3"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"113998","DOI":"10.1016\/j.addr.2021.113998","article-title":"Ultrasonic particles: An approach for targeted gene delivery","volume":"179","author":"Walsh","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/sj.gt.3301624","article-title":"Magnetofection: Enhancing and targeting gene delivery by magnetic force in vitro and in vivo","volume":"9","author":"Scherer","year":"2002","journal-title":"Gene Ther."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Prosen, L., Prijic, S., Music, B., Lavrencak, J., Cemazar, M., and Sersa, G. (2013). Magnetofection: A Reproducible Method for Gene Delivery to Melanoma Cells. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/209452"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s40290-021-00417-5","article-title":"Delivery Strategies for mRNA Vaccines","volume":"36","author":"Ramachandran","year":"2022","journal-title":"Pharm. Med."},{"key":"ref_175","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_176","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/sj.gt.3302964","article-title":"Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent","volume":"14","author":"Probst","year":"2007","journal-title":"Gene Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"eabc7804","DOI":"10.1126\/scitranslmed.abc7804","article-title":"Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models","volume":"13","author":"Hotz","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1080\/1061186X.2018.1550646","article-title":"Precise tuning of disulphide crosslinking in mRNA polyplex micelles for optimising extracellular and intracellular nuclease tolerability","volume":"27","author":"Dirisala","year":"2019","journal-title":"J. Drug Target."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/pj.2014.50","article-title":"Design of gene-activated matrix for the repair of skin and cartilage","volume":"46","author":"Wang","year":"2014","journal-title":"Polym. J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1038\/sj.mt.6300314","article-title":"Hydrodynamic Gene Delivery: Its Principles and Applications","volume":"15","author":"Suda","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/sj.gt.3302210","article-title":"Hydroporation as the mechanism of hydrodynamic delivery","volume":"11","author":"Zhang","year":"2004","journal-title":"Gene Ther."},{"key":"ref_182","unstructured":"(2023, July 04). IMLYGIC, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/imlygic."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.omtm.2019.01.010","article-title":"EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation","volume":"13","author":"Detela","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_184","unstructured":"(2023, July 04). LUXTURNA, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/luxturna."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Beheshtizadeh, N., Gharibshahian, M., Pazhouhnia, Z., Rostami, M., Rajabi Zangi, A., Maleki, R., Kolahi Azar, H., Zalouli, V., Rajavand, H., and Farzin, A. (2022). Commercialization and regulation of regenerative medicine products: Promises, advances and challenges. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113431"},{"key":"ref_186","unstructured":"(2023, July 04). ZOLGENSMA, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/zolgensma."},{"key":"ref_187","unstructured":"(2023, July 04). Spinraza. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/spinraza."},{"key":"ref_188","unstructured":"(2023, July 04). Onpattro. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/onpattro."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1089\/hum.2017.218","article-title":"The First Approved Gene Therapy Product for Cancer Ad-p53 (Gendicine): 12 Years in the Clinic","volume":"29","author":"Zhang","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_190","unstructured":"Zhang, S.-Y., Lu, Y.-Y., and Peng, Z.-H. (2012). Recent Advances in Cancer Research and Therapy, Elsevier."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"287","DOI":"10.21103\/Article10(3)_ShC1","article-title":"The Experience of Using \u201cNeovasculgen\u201d in the Complex Treatment of Patients with Critical Lower Limb Ischemia","volume":"10","author":"Vinokurov","year":"2020","journal-title":"Int. J. Biomed."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.3389\/fonc.2020.01786","article-title":"The Oncolytic Virus in Cancer Diagnosis and Treatment","volume":"10","author":"Cao","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2174\/1568009618666171129221503","article-title":"Oncorine, the World First Oncolytic Virus Medicine and its Update in China","volume":"18","author":"Liang","year":"2018","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_194","unstructured":"(2023, July 04). Defitelio. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/defitelio."},{"key":"ref_195","unstructured":"(2023, July 04). ADSTILADRIN, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/adstiladrin."},{"key":"ref_196","unstructured":"(2023, July 04). Package Insert\u2014ADSTILADRIN, Available online: https:\/\/www.fda.gov\/media\/164029\/download."},{"key":"ref_197","unstructured":"(2023, July 04). Hemgenix. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/hemgenix."},{"key":"ref_198","unstructured":"(2023, July 04). HEMGENIX, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/vaccines\/hemgenix."},{"key":"ref_199","unstructured":"(2023, July 04). Package Insert\u2014HEMGENIX, Available online: https:\/\/www.fda.gov\/media\/163467\/download."},{"key":"ref_200","unstructured":"(2023, July 04). Upstaza. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/upstaza."},{"key":"ref_201","unstructured":"(2023, July 04). Upstaza (Eladocagene Exuparvovec). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/overview\/upstaza-epar-medicine-overview_en.pdf."},{"key":"ref_202","unstructured":"(2023, July 04). Abecma\u2014Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/abecma-epar-product-information_en.pdf."},{"key":"ref_203","unstructured":"(2023, July 04). ABECMA (Idecabtagene Vicleucel), Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/abecma-idecabtagene-vicleucel."},{"key":"ref_204","unstructured":"(2023, July 04). Approval Letter\u2014ABECMA, Available online: https:\/\/www.fda.gov\/media\/147062\/download."},{"key":"ref_205","unstructured":"(2023, July 04). Abecma. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/abecma."},{"key":"ref_206","unstructured":"(2023, July 04). Carvykti. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/carvykti."},{"key":"ref_207","unstructured":"(2023, July 04). Carvykti\u2014Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/carvykti-epar-product-information_en.pdf."},{"key":"ref_208","unstructured":"(2023, July 04). Approval Letter\u2014CARVYKTI, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/carvykti."},{"key":"ref_209","unstructured":"(2023, July 04). Package Insert\u2014CARVYKTI, Available online: https:\/\/www.fda.gov\/media\/156560\/download."},{"key":"ref_210","unstructured":"(2023, July 04). Approval Letter\u2014SKYSONA, Available online: https:\/\/www.fda.gov\/media\/161665\/download."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1302\/2046-3758.810.BJR-2019-0265","article-title":"The vicissitudes of gene therapy","volume":"8","author":"Evans","year":"2019","journal-title":"Bone Joint Res."},{"key":"ref_212","unstructured":"(2023, July 04). Skysona, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/skysona."},{"key":"ref_213","unstructured":"(2023, July 04). YESCARTA (Axicabtagene Ciloleucel), Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/yescarta-axicabtagene-ciloleucel."},{"key":"ref_214","unstructured":"(2023, July 04). Package Insert\u2014YESCARTA (Axicabtagene Ciloleucel), Available online: https:\/\/www.fda.gov\/media\/108377\/download."},{"key":"ref_215","unstructured":"(2023, July 04). KYMRIAH (Tisagenlecleucel), Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/kymriah-tisagenlecleucel."},{"key":"ref_216","unstructured":"(2023, July 04). Kymriah. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/kymriah."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Labb\u00e9, R.P., Vessillier, S., and Rafiq, Q.A. (2021). Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives. Viruses, 13.","DOI":"10.3390\/v13081528"},{"key":"ref_218","unstructured":"(2023, July 04). Strimvelis. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/strimvelis."},{"key":"ref_219","unstructured":"(2023, July 04). Breyanzi. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/breyanzi."},{"key":"ref_220","unstructured":"(2023, July 04). Breyanzi. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/breyanzi-epar-product-information_en.pdf."},{"key":"ref_221","unstructured":"(2023, July 04). Breyanzi (Lisocabtagene Maraleucel), Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/breyanzi-lisocabtagene-maraleucel."},{"key":"ref_222","unstructured":"(2023, July 04). Tecartus (Brexucabtagene Autoleucel), Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/tecartus-brexucabtagene-autoleucel."},{"key":"ref_223","unstructured":"(2023, July 04). Tecartus. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/tecartus."},{"key":"ref_224","unstructured":"(2023, July 04). Zynteglo, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/zynteglo."},{"key":"ref_225","unstructured":"(2023, July 04). Libmeldy. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/libmeldy."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Ganesan, L.P., Mohanty, S., Kim, J., Clark, K.R., Robinson, J.M., and Anderson, C.L. (2011). Rapid and Efficient Clearance of Blood-borne Virus by Liver Sinusoidal Endothelium. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002281"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"eabb8133","DOI":"10.1126\/sciadv.abb8133","article-title":"Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines","volume":"6","author":"Dirisala","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41551-019-0378-3","article-title":"Visualization of early events in mRNA vaccine delivery in non-human primates via PET\u2013CT and near-infrared imaging","volume":"3","author":"Lindsay","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"e2207841119","DOI":"10.1073\/pnas.2207841119","article-title":"Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response","volume":"119","author":"Chen","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jconrel.2021.12.027","article-title":"Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE)","volume":"344","author":"Parhiz","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Dirisala, A., Li, J., Gonzalez-Carter, D., and Wang, Z. (2023). Editorial: Delivery systems in biologics-based therapeutics. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1274210"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/10\/1416\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:05:26Z","timestamp":1760130326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/10\/1416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":231,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ph16101416"],"URL":"https:\/\/doi.org\/10.3390\/ph16101416","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,5]]}}}