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Purif."},{"key":"10.1016\/j.ymthe.2026.07.020_bib79","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1101\/gr.224964.117","article-title":"Deep learning of the regulatory grammar of yeast 5' untranslated regions from 500,000 random sequences","volume":"27","author":"Cuperus","year":"2017","journal-title":"Genome Res."},{"key":"10.1016\/j.ymthe.2026.07.020_bib80","doi-asserted-by":"crossref","first-page":"975","DOI":"10.7150\/ijms.71840","article-title":"Advances in Circular RNA and Its Applications","volume":"19","author":"Zhao","year":"2022","journal-title":"Int. J. Med. Sci."},{"key":"10.1016\/j.ymthe.2026.07.020_bib81","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41587-022-01393-0","article-title":"Engineering circular RNA for enhanced protein production","volume":"41","author":"Chen","year":"2023","journal-title":"Nat. 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Rev."},{"key":"10.1016\/j.ymthe.2026.07.020_bib109","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.immuni.2011.05.003","article-title":"Immune signaling by RIG-I-like receptors","volume":"34","author":"Loo","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2026.07.020_bib110","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2021.101262","article-title":"Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial","volume":"44","author":"Pollock","year":"2022","journal-title":"EClinicalMedicine"},{"key":"10.1016\/j.ymthe.2026.07.020_bib111","article-title":"A Phase 1\/2 Randomised, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Immunogenicity of ARCT-021 in Healthy Adult Subjects","author":"Low","year":"2021","journal-title":"medRxiv"},{"key":"10.1016\/j.ymthe.2026.07.020_bib112","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.ymthe.2020.11.011","article-title":"Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA","volume":"29","author":"Blakney","year":"2021","journal-title":"Mol. 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USA"},{"key":"10.1016\/j.ymthe.2026.07.020_bib125","doi-asserted-by":"crossref","first-page":"28311","DOI":"10.1021\/acsnano.4c09677","article-title":"Amplification of Protein Expression by Self-Amplifying mRNA Delivered in Lipid Nanoparticles Containing a \u03b2-Aminoester Ionizable Lipid Correlates with Reduced Innate Immune Activation","volume":"18","author":"De Lombaerde","year":"2024","journal-title":"ACS nano"},{"key":"10.1016\/j.ymthe.2026.07.020_bib126","doi-asserted-by":"crossref","DOI":"10.1016\/j.jconrel.2025.113617","article-title":"Investigation of the impact of lipid nanoparticle compositions on the delivery and T cell response of circRNA vaccine","volume":"381","author":"Alshehry","year":"2025","journal-title":"J. Control Release"},{"key":"10.1016\/j.ymthe.2026.07.020_bib127","doi-asserted-by":"crossref","DOI":"10.1002\/adma.201801151","article-title":"Ionizable Amino-Polyesters Synthesized via Ring Opening Polymerization of Tertiary Amino-Alcohols for Tissue Selective mRNA Delivery","volume":"30","author":"Kowalski","year":"2018","journal-title":"Adv. Mater."},{"key":"10.1016\/j.ymthe.2026.07.020_bib128","doi-asserted-by":"crossref","first-page":"108","DOI":"10.20885\/ijca.vol7.iss2.art9","article-title":"Advances in Mesoporous Silica Nanoparticles: Synthesis, Characterization, and Biomedical Uses","volume":"7","author":"Saputra","year":"2024","journal-title":"Ind. J. Chem. Anal."},{"key":"10.1016\/j.ymthe.2026.07.020_bib129","doi-asserted-by":"crossref","first-page":"991","DOI":"10.3390\/ph5090991","article-title":"Applications of cell-penetrating peptides for tumor targeting and future cancer therapies","volume":"5","author":"Regberg","year":"2012","journal-title":"Pharmaceuticals (Basel, Switzerland)"},{"key":"10.1016\/j.ymthe.2026.07.020_bib130","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41577-026-01273-7","article-title":"Harnessing mucosal immunity for protective vaccines","volume":"26","author":"Kwon","year":"2026","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.020_bib131","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.jconrel.2023.09.031","article-title":"Spray dried lipid nanoparticle formulations enable intratracheal delivery of mRNA","volume":"363","author":"Friis","year":"2023","journal-title":"J. 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Nanomedicine"},{"key":"10.1016\/j.ymthe.2026.07.020_bib134","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejpb.2025.114811","article-title":"Powder-attached microneedles for the stable and effective transdermal delivery of clinically validated mRNA-LNP vaccine","volume":"214","author":"Kim","year":"2025","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ymthe.2026.07.020_bib135","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1038\/s41467-024-45422-9","article-title":"High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models","volume":"15","author":"Xue","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.07.020_bib136","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202514370","article-title":"High-Throughput In Vivo Screening Using Barcoded mRNA Identifies Lipid Nanoparticles With Extrahepatic Tropism for In Situ Immunoengineering","volume":"38","author":"Hamilton","year":"2026","journal-title":"Adv. Mater."},{"key":"10.1016\/j.ymthe.2026.07.020_bib137","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1021\/acs.molpharmaceut.2c00587","article-title":"Leveraging Biological Buffers for Efficient Messenger RNA Delivery via Lipid Nanoparticles","volume":"19","author":"Henderson","year":"2022","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.ymthe.2026.07.020_bib138","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.xphs.2021.11.004","article-title":"pH-Dependent Phase Behavior and Stability of Cationic Lipid-mRNA Nanoparticles","volume":"111","author":"Larson","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ymthe.2026.07.020_bib139","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.xphs.2024.12.013","article-title":"Recent advances in drying and development of solid formulations for stable mRNA and siRNA lipid nanoparticles","volume":"114","author":"Arte","year":"2025","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ymthe.2026.07.020_bib140","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejpb.2023.11.007","article-title":"Evaluation of the effects of storage conditions on spray-dried siRNA-LNPs before and after subsequent drying","volume":"193","author":"Zimmermann","year":"2023","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ymthe.2026.07.020_bib141","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.xphs.2022.11.001","article-title":"The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case","volume":"112","author":"Oude Blenke","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ymthe.2026.07.020_bib142","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1038\/mt.2014.133","article-title":"A cationic nanoemulsion for the delivery of next-generation RNA vaccines","volume":"22","author":"Brito","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2026.07.020_bib143","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.omtm.2022.03.009","article-title":"A flexible, thermostable nanostructured lipid carrier platform for RNA vaccine delivery. Molecular therapy","volume":"25","author":"Gerhardt","year":"2022","journal-title":"Mol. Ther. Methods Clin. 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