Современные материалы для невирусных систем доставки в генной терапии

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Опубликован: Mar 23, 2026
DOI: https://doi.org/10.18097/BMCRM00287
Ключевые слова:
генная терапия; вектор; невирусные системы доставки; липидный вектор; поликатионный вектор

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А.В. Раднаева
Центр регенеративной медицины, Медицинский научно-образовательный институт, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1; Факультет фундаментальной медицины, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1
Е.А. Слободкина
Центр регенеративной медицины, Медицинский научно-образовательный институт, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1
В.А. Ткачук
Центр регенеративной медицины, Медицинский научно-образовательный институт, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1; Факультет фундаментальной медицины, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1; Национальный медицинский исследовательский центр кардиологии имени акад. Е.И. Чазова, 121552, Москва, ул. Академика Чазова, 15А
П.И. Макаревич
Центр регенеративной медицины, Медицинский научно-образовательный институт, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1; Факультет фундаментальной медицины, Московский государственный университет имени М.В. Ломоносова, 119234, Москва, ул. Ленинские Горы, 1; Национальный медицинский исследовательский центр кардиологии имени акад. Е.И. Чазова, 121552, Москва, ул. Академика Чазова, 15А

Аннотация

Современные системы доставки генетического материала делятся на вирусные и невирусные. Несмотря на доминирование вирусных векторов в разработках препаратов для генной терапии из-за высокой эффективности трансдукции, их применение ограничено иммуногенностью, риском инсерционного мутагенеза и воспалительными реакциями. Невирусные системы обладают лучшим профилем безопасности, возможностью масштабируемого производства и гибкостью в нагрузке генетическим материалом, но уступают в эффективности трансфекции. Основные проблемы, влияющие на трансфекцию невирусными векторами, заключаются в низкой стабильности нуклеиновых кислот in vivo, сложности доставки материала в ядро клетки и токсичности химических соединений, входящих в конструкцию вектора. Для решения проблем низкой эффективности доставки генетического материала невирусными векторными системами необходимо направить дальнейшие исследования на оптимизацию химической структуры молекул-носителей, их модификации для улучшения таргетинга и на детальное изучения внутриклеточных путей транспорта векторов. Наиболее перспективными областями применения невирусных систем доставки на сегодняшний момент являются онкология, разработка вакцин и легочные заболевания.

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Как цитировать
Раднаева A., Слободкина E., Ткачук V., & Макаревич P. (2026). Современные материалы для невирусных систем доставки в генной терапии. Biomedical Chemistry: Research and Methods, 9(1), e00287. https://doi.org/10.18097/BMCRM00287
Выпуск
Том 9 № 1 (2026): Принято в печать
Раздел
ОБЗОРЫ

Библиографические ссылки

  1. American Society of Gene &Cell Therapy (ASGCT). ASGCT-Citeline Q2 2025 Report. Retrieved from: https://www.asgct.org/news-publications/ landscape-report
  2. Asokan, A. (2023). AAV vector immunotoxicity: Stopping the domino effect. Molecular Therapy: The Journal of the American Society of Gene Therapy, 31(12), 3357–3358. DOI
  3. Nayak, S., & Herzog, R. W. (2010). Progress and prospects: Immune responses to viral vectors. Gene Therapy, 17(3), 295–304. DOI
  4. Vranckx, L. S., Demeulemeester, J., Debyser, Z., & Gijsbers, R. (2016). Towards a Safer, More Randomized Lentiviral Vector Integration Profile Exploring Artificial LEDGF Chimeras. PLOS ONE, 11(10), e0164167. DOI
  5. Hidai, C., & Kitano, H. (2018). Nonviral Gene Therapy for Cancer: A Review. Diseases, 6(3), 57. DOI
  6. Li, S.,Huang, L. (2000) Nonviral gene therapy: promises and challenges. Gene Therapy, 7(1), 31-4. DOI
  7. Bartsch, M., Weeke-Klimp, A. H., Hoenselaar, E. P. D., Stuart, M. C. A., Meijer, D. K. F., Scherphof, G. L., & Kamps, J. A. A. M. (2004). Stabilized Lipid Coated Lipoplexes for the Delivery of Antisense Oligonucleotides to Liver Endothelial Cells In Vitro and In Vivo. Journal of Drug Targeting, 12(9–10), 613–621. DOI
  8. Hildebrandt, I. J., Iyer, M., Wagner, E., & Gambhir, S. S. (2003). Optical imaging of transferrin targeted PEI/DNA complexes in living subjects. Gene Therapy, 10(9), 758–764. DOI
  9. Yu, W., Pirollo, K., Rait, A., Yu, B., Xiang, L., Huang, W., Zhou, Q., Ertem, G., & Chang, E. (2004). A sterically stabilized immunolipoplex for systemic administration of a therapeutic gene. Gene Therapy, 11(19), 1434–1440. DOI
  10. Zu, H., & Gao, D. (2021). Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects. The AAPS Journal, 23(4), 78. DOI
  11. Frolov, V. A., Shnyrova, A. V., & Zimmerberg, J. (2011). Lipid Polymorphisms and Membrane Shape. Cold Spring Harbor Perspectives in Biology, 3(11), a004747–a004747. DOI
  12. Zhi, D., Bai, Y., Yang, J., Cui, S., Zhao, Y., Chen, H., & Zhang, S. (2018). A review on cationic lipids with different linkers for gene delivery. Advances in Colloid and Interface Science, 253, 117–140. DOI
  13. Tseu, G. Y. W., & 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(3), 1498. DOI
  14. Chatterjee, S., Kon, E., Sharma, P., & Peer, D. (2024). Endosomal escape: A bottleneck for LNP-mediated therapeutics. Proceedings of the National Academy of Sciences, 121(11), e2307800120. DOI
  15. Liu, Z., Wu, J., Wang, N., Lin, Y., Song, R., Zhang, M., & Li, B. (2025). Structure-guided design of endosomolytic chloroquine-like lipid nanoparticles for mRNA delivery and genome editing. Nature Communications, 16(1), 4241. DOI
  16. Dowdy, S. F. (2023). Endosomal escape of RNA therapeutics: How do we solve this rate-limiting problem? RNA (New York, N.Y.), 29(4), 396–401. DOI
  17. Cui, S., Wang, Y., Gong, Y., Lin, X., Zhao, Y., Zhi, D., Zhou, Q., & Zhang, S. (2018). Correlation of the cytotoxic effects of cationic lipids with their headgroups. Toxicology Research, 7(3), 473–479. DOI
  18. Dokka, S., Toledo, D., Shi, X., Castranova, V., & Rojanasakul, Y. (2000). Oxygen Radical-Mediated Pulmonary Toxicity Induced by Some Cationic Liposomes. Pharmaceutical Research, 17(5), 521–525. DOI
  19. Haghiralsadat, F., Amoabediny, G., Naderinezhad, S., Forouzanfar, T., Helder, M. N., & Zandieh-Doulabi, B. (2018). Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup1), 684–692. DOI
  20. Kapoor, M., & Burgess, D. J. (2012). Efficient and safe delivery of siRNA using anionic lipids: Formulation optimization studies. International Journal of Pharmaceutics, 432(1–2), 80–90. DOI
  21. Malone, R. W., Felgner, P. L., & Verma, I. M. (1989). Cationic liposomemediated RNA transfection. Proceedings of the National Academy of Sciences, 86(16), 6077–6081. DOI
  22. Felgner, J., Martin, M., Tsai, Y., & Felgner, P. L. (1993). Cationic lipidmediated transfection in mammalian cells: “Lipofection”. Journal of Tissue Culture Methods, 15(2), 63–68. DOI
  23. Kranz, L. M., Diken, M., Haas, H., Kreiter, S., Loquai, C., Reuter, K. C., Meng, M., Fritz, D., Vascotto, F., Hefesha, H., Grunwitz, C., Vormehr, M., Hüsemann, Y., Selmi, A., Kuhn, A. N., Buck, J., Derhovanessian, E., Rae, R., Attig, S., … Sahin, U. (2016). Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature, 534(7607), 396–401. DOI
  24. Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., Akilli-Öztürk, Ö., Kranz, L. M., Berger, H., Petschenka, J., Diken, M., Kreiter, S., Yogev, N., Waisman, A., Karikó, K., Türeci, Ö., & Sahin, U. (2021). A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, 371(6525), 145–153. DOI
  25. Wang, J., Ding, Y., Chong, K., Cui, M., Cao, Z., Tang, C., Tian, Z., Hu, Y., Zhao, Y., & Jiang, S. (2024). Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery. Vaccines, 12(10), 1148. DOI
  26. Giulimondi, F., Digiacomo, L., Pozzi, D., Palchetti, S., Vulpis, E., Capriotti, A. L., Chiozzi, R. Z., Laganà, A., Amenitsch, H., Masuelli, L., Peruzzi, G., Mahmoudi, M., Screpanti, I., Zingoni, A., & Caracciolo, G. (2019). Interplay of protein corona and immune cells controls blood residency of liposomes. Nature Communications, 10(1), 3686. DOI
  27. Chen, Z., Place, R. F., Jia, Z.-J., Pookot, D., Dahiya, R., & Li, L.-C. (2008). Antitumor effect of dsRNA-induced p21WAF1/CIP1 gene activation in human bladder cancer cells. Molecular Cancer Therapeutics, 7(3), 698–703. DOI
  28. Akhtar, S., Basu, S., Wickstrom, E., & Juliano, R. L. (1991). Interactions of antisense DNa oliginucletide analogs with phospholid membranes (liposomes). Nucleic Acids Research, 19(20), 5551–5559. DOI
  29. Wan, Y., Dai, W., Nevagi, R. J., Toth, I., & Moyle, P. M. (2017). Multifunctional peptide-lipid nanocomplexes for efficient targeted delivery of DNA and siRNA into breast cancer cells. Acta Biomaterialia, 59, 257–268. DOI
  30. Bozzuto, G., & Molinari, A. (2015). Liposomes as nanomedical devices. International Journal of Nanomedicine, 975. DOI
  31. Lasic, D. D. (2019). LIPOSOMES in GENE DELIVERY (1-e изд.). CRC Press. DOI
  32. Ibaraki, H., Takeda, A., Arima, N., Hatakeyama, N., Takashima, Y., Seta, Y., & Kanazawa, T. (2021). In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification. Pharmaceutics, 13(1), 104. DOI
  33. Zuhorn, I. S., Bakowsky, U., Polushkin, E., Visser, W. H., Stuart, M. C. A., Engberts, J. B. F. N., & Hoekstra, D. (2005). Nonbilayer phase of lipoplex–membrane mixture determines endosomal escape of genetic cargo and transfection efficiency. Molecular Therapy, 11(5), 801–810. DOI
  34. Farid, M., Faber, T., Dietrich, D., & Lamprecht, A. (2020). Cell membrane fusing liposomes for cytoplasmic delivery in brain endothelial cells. Colloids and Surfaces B: Biointerfaces, 194, 111193. DOI
  35. François-Martin, C., Bacle, A., Rothman, J. E., Fuchs, P. F. J., & Pincet, F. (2021). Cooperation of Conical and Polyunsaturated Lipids to Regulate Initiation and Processing of Membrane Fusion. Frontiers in Molecular Biosciences, 8, 763115. DOI
  36. Pisani, M., Mobbili, G., & Bruni, P. (2011). Neutral Liposomes and DNA Transfection. B X. Yuan (Peд.), Non-Viral Gene Therapy. InTech. DOI
  37. Wang, M. M., Wappelhorst, C. N., Jensen, E. L., Chi, Y.-C. T., Rouse, J. C., & Zou, Q. (2023). Elucidation of lipid nanoparticle surface structure in mRNA vaccines. Scientific Reports, 13(1), 16744. DOI
  38. Biswal, M. R., Roy, S., & Singh, J. K. (2024). Comparative Analysis of Lipid Nanoparticles in Pfizer-BioNTech and Moderna COVID-19 Vaccines: Insights from Molecular Dynamics Simulations. Biophysics. DOI
  39. Paunovska, K., Gil, C. J., Lokugamage, M. P., Sago, C. D., Sato, M., Lando, G. N., Gamboa Castro, M., Bryksin, A. V., & Dahlman, J. E. (2018). Analyzing 2000 in Vivo Drug Delivery Data Points Reveals Cholesterol Structure Impacts Nanoparticle Delivery. ACS Nano, 12(8), 8341–8349. DOI
  40. Paunovska, K., Da Silva Sanchez, A. J., Sago, C. D., Gan, Z., Lokugamage, M. P., Islam, F. Z., Kalathoor, S., Krupczak, B. R., & Dahlman, J. E. (2019). Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses. Advanced Materials, 31(14), 1807748. DOI
  41. Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M., & Danielsen, M. (1987). Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure. Proceedings of the National Academy of Sciences, 84(21), 7413–7417. DOI
  42. Suk, J. S., Xu, Q., Kim, N., Hanes, J., & Ensign, L. M. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews, 99, 28–51. DOI
  43. Samaridou, E., Heyes, J., & Lutwyche, P. (2020). Lipid nanoparticles for nucleic acid delivery: Current perspectives. Advanced Drug Delivery Reviews, 154–155, 37–63. DOI
  44. Han, X., Zhang, H., Butowska, K., Swingle, K. L., Alameh, M.-G., Weissman, D., & Mitchell, M. J. (2021). An ionizable lipid toolbox for RNA delivery. Nature Communications, 12(1), 7233. DOI
  45. Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., Judge, A. D., Lam, K., McClintock, K., Nechev, L. V., Palmer, L. R., Racie, T., Röhl, I., Seiffert, S., Shanmugam, S., … MacLachlan, I. (2006). RNAi-mediated gene silencing in non-human primates. Nature, 441(7089), 111–114. DOI
  46. Akinc, A., Maier, M. A., Manoharan, M., Fitzgerald, K., Jayaraman, M., Barros, S., Ansell, S., Du, X., Hope, M. J., Madden, T. D., Mui, B. L., Semple, S. C., Tam, Y. K., Ciufolini, M., Witzigmann, D., Kulkarni, J. A., Van Der Meel, R., & Cullis, P. R. (2019). The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nature Nanotechnology, 14(12), 1084–1087. DOI
  47. Tesei, G., Hsiao, Y.-W., Dabkowska, A., Grönberg, G., Yanez Arteta, M., Ulkoski, D., Bray, D. J., Trulsson, M., Ulander, J., Lund, M., & Lindfors, L. (2024). Lipid shape and packing are key for optimal design of pH-sensitive mRNA lipid nanoparticles. Proceedings of the National Academy of Sciences, 121(2), e2311700120. DOI
  48. Cheng, Q., Wei, T., Farbiak, L., Johnson, L. T., Dilliard, S. A., & Siegwart, D. J. (2020). Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nature Nanotechnology, 15(4), 313–320. DOI
  49. Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., Butler, J. S., Qin, L., Racie, T., Sprague, A., Fava, E., Zeigerer, A., Hope, M. J., Zerial, M., Sah, D. W., … Maier, M. A. (2010). Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms. Molecular Therapy, 18(7), 1357–1364. DOI
  50. Wittrup, A., Ai, A., Liu, X., Hamar, P., Trifonova, R., Charisse, K., Manoharan, M., Kirchhausen, T., & Lieberman, J. (2015). Visualizing lipidformulated siRNA release from endosomes and target gene knockdown. Nature Biotechnology, 33(8), 870–876. DOI
  51. Gilleron, J., Querbes, W., Zeigerer, A., Borodovsky, A., Marsico, G., Schubert, U., Manygoats, K., Seifert, S., Andree, C., Stöter, M., Epstein-Barash, H., Zhang, L., Koteliansky, V., Fitzgerald, K., Fava, E., Bickle, M., Kalaidzidis, Y., Akinc, A., Maier, M., & Zerial, M. (2013). Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape. Nature Biotechnology, 31(7), 638–646. DOI
  52. Johansson, J. M., Du Rietz, H., Hedlund, H., Eriksson, H. C., Oude Blenke, E., Pote, A., Harun, S., Nordenfelt, P., Lindfors, L., & Wittrup, A. (2024). Cellular and biophysical barriers to lipid nanoparticle mediated delivery of RNA to the cytosol. Bioengineering. DOI
  53. Maugeri, M., Nawaz, M., Papadimitriou, A., Angerfors, A., Camponeschi, A., Na, M., Hölttä, M., Skantze, P., Johansson, S., Sundqvist, M., Lindquist, J., Kjellman, T., Mårtensson, I.-L., Jin, T., Sunnerhagen, P., Östman, S., Lindfors, L., & Valadi, H. (2019). Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells. Nature Communications, 10(1), 4333. DOI
  54. Jörgensen, A. M., Wibel, R., & Bernkop-Schnürch, A. (2023). Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients. Small, 19(17), 2206968. DOI
  55. Suzuki, Y., & Ishihara, H. (2021). Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs. Drug Metabolism and Pharmacokinetics, 41, 100424. DOI
  56. Couture-Senécal, J., Tilstra, G., & Khan, O. F. (2024). Engineering ionizable lipids for rapid biodegradation balances mRNA vaccine efficacy and tolerability. Bioengineering. DOI
  57. Wang, C., Xue, Y., Markovic, T., Li, H., Wang, S., Zhong, Y., Du, S., Zhang, Y., Hou, X., Yu, Y., Liu, Z., Tian, M., Kang, D. D., Wang, L., Guo, K., Cao, D., Yan, J., Deng, B., McComb, D. W., … Dong, Y. (2025). Blood–brain-barriercrossing lipid nanoparticles for mRNA delivery to the central nervous system. Nature Materials. DOI
  58. Ly, P.-D., Ly, K.-N., Phan, H.-L., Nguyen, H. H. T., Duong, V.-A., & Nguyen, H. V. (2024). Recent advances in surface decoration of nanoparticles in drug delivery. Frontiers in Nanotechnology, 6, 1456939. DOI
  59. Patel, M. N., Tiwari, S., Wang, Y., O’Neill, S., Wu, J., Omo-Lamai, S., Espy, C., Chase, L. S., Majumder, A., Hoffman, E., Shah, A., Sárközy, A., Katzen, J., Pardi, N., & Brenner, J. S. (2025). Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids. Nature Biotechnology. DOI
  60. Lungu, C., Diudea, M., Putz, M., & Grudziński, I. (2016). Linear and Branched PEIs (Polyethylenimines) and Their Property Space. International Journal of Molecular Sciences, 17(4), 555. DOI
  61. Kaksonen, M., & Roux, A. (2018). Mechanisms of clathrin-mediated endocytosis. Nature Reviews Molecular Cell Biology, 19(5), 313–326. DOI
  62. Oh, Y.-K., Suh, D., Kim, J. M., Choi, H.-G., Shin, K., & Ko, J. J. (2002). Polyethylenimine-mediated cellular uptake, nucleus trafficking and expression of cytokine plasmid DNA. Gene Therapy, 9(23), 1627–1632. DOI
  63. Ochrimenko, S., Vollrath, A., Tauhardt, L., Kempe, K., Schubert, S., Schubert, U. S., & Fischer, D. (2014). Dextran-graft-linear poly(ethylene imine) s for gene delivery: Importance of the linking strategy. Carbohydrate Polymers, 113, 597–606. DOI
  64. Yamada, H., Loretz, B., & Lehr, C.-M. (2014). Design of Starch- graft -PEI Polymers: An Effective and Biodegradable Gene Delivery Platform. Biomacromolecules, 15(5), 1753–1761. DOI
  65. Nicolle, L., Casper, J., Willimann, M., Journot, C. M. A., Detampel, P., Einfalt, T., Grisch-Chan, H. M., Thöny, B., Gerber-Lemaire, S., & Huwyler, J. (2021). Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation. International Journal of Molecular Sciences, 22(8), 3828. DOI
  66. Ma, K., Hu, M., Qi, Y., Qiu, L., Jin, Y., Yu, J., & Li, B. (2009). Structure– transfection activity relationships with glucocorticoid–polyethyl-enimine conjugate nuclear gene delivery systems. Biomaterials, 30(22), 3780–3789. DOI
  67. Wu, P., Luo, X., Wu, H., Zhang, Q., Wang, K., Sun, M., & Oupicky, D. (2020). Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery. Bioconjugate Chemistry, 31(3), 698–707. DOI
  68. Dunn, A. W., Kalinichenko, V. V., & Shi, D. (2018). Highly Efficient In Vivo Targeting of the Pulmonary Endothelium Using Novel Modifications of Polyethylenimine: An Importance of Charge. Advanced Healthcare Materials, 7(23), 1800876. DOI
  69. Ito, T., Yoshihara, C., Hamada, K., & Koyama, Y. (2010). DNA/ polyethyleneimine/hyaluronic acid small complex particles and tumor suppression in mice. Biomaterials, 31(10), 2912–2918. DOI
  70. Russ, V., Elfberg, H., Thoma, C., Kloeckner, J., Ogris, M., & Wagner, E. (2008). Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer. Gene Therapy, 15(1), 18–29. DOI
  71. Yu, H., Russ, V., & Wagner, E. (2009). Influence of the Molecular Weight of Bioreducible Oligoethylenimine Conjugates on the Polyplex Transfection Properties. The AAPS Journal, 11(3), 445. DOI
  72. Xu, S., Chen, M., Yao, Y., Zhang, Z., Jin, T., Huang, Y., & Zhu, H. (2008). Novel poly(ethylene imine) biscarbamate conjugate as an efficient and nontoxic gene delivery system. Journal of Controlled Release, 130(1), 64–68. DOI
  73. Kim, Y. H., Park, J. H., Lee, M., Kim, Y.-H., Park, T. G., & Kim, S. W. (2005). Polyethylenimine with acid-labile linkages as a biodegradable gene carrier. Journal of Controlled Release, 103(1), 209–219. DOI
  74. Fang, G., Zeng, F., Yu, C., & Wu, S. (2014). Low molecular weight PEIs modified by hydrazone-based crosslinker and betaine as improved gene carriers. Colloids and Surfaces B: Biointerfaces, 122, 472–481. DOI
  75. Xiong, M. P., Laird Forrest, M., Ton, G., Zhao, A., Davies, N. M., & Kwon, G. S. (2007). Poly(aspartate-g-PEI800), a polyethylenimine analogue of low toxicity and high transfection efficiency for gene delivery. Biomaterials, 28(32), 4889–4900. DOI
  76. Buscail, L., Bournet, B., Vernejoul, F., Cambois, G., Lulka, H., Hanoun, N., Dufresne, M., Meulle, A., Vignolle-Vidoni, A., Ligat, L., Saint-Laurent, N., Pont, F., Dejean, S., Gayral, M., Martins, F., Torrisani, J., Barbey, O., Gross, F., Guimbaud, R., … Cordelier, P. (2015). First-in-man Phase 1 Clinical Trial of Gene Therapy for Advanced Pancreatic Cancer: Safety, Biodistribution, and Preliminary Clinical Findings. Molecular Therapy, 23(4), 779–789. DOI
  77. Meleshko, A. N., Petrovskaya, N. A., Savelyeva, N., Vashkevich, K. P., Doronina, S. N., & Sachivko, N. V. (2017). Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma. Human Vaccines & Immunotherapeutics, 13(6), 1398–1403. DOI
  78. Thaker, P. H., Brady, W. E., Lankes, H. A., Odunsi, K., Bradley, W. H., Moore, K. N., Muller, C. Y., Anwer, K., Schilder, R. J., Alvarez, R. D., & Fracasso, P. M. (2017). A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group study. Gynecologic Oncology, 147(2), 283–290. DOI
  79. Halachmi, S., Leibovitch, I., Zisman, A., Stein, A., Benjamin, S., Sidi, A., Knickerbocker, R., Limor, M., & Moore, Y. (2018). Phase II trial of BC-819 intravesical gene therapy in combination with BCG in patients with non-muscle invasive bladder cancer (NMIBC). Journal of Clinical Oncology, 36(6_suppl), 499–499. DOI
  80. A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-1944 in Healthy Adults: Phase 1/2a clinical trial NCT03719300. Sponsor: ModernaTX, Inc. (2018–2021). Retrieved from: https://clinicaltrials.gov/study/NCT03719300
  81. Gofrit, O. N., Benjamin, S., Halachmi, S., Leibovitch, I., Dotan, Z., Lamm, D. L., Ehrlich, N., Yutkin, V., Ben-Am, M., & Hochberg, A. (2014). DNA Based Therapy with Diphtheria Toxin-A BC-819: A Phase 2b Marker Lesion Trial in Patients with Intermediate Risk Nonmuscle Invasive Bladder Cancer. Journal of Urology, 191(6), 1697–1702. DOI
  82. A Phase 1, First-in-Human, Open-Label, Dose-Escalation Study of mRNA- 2752, a Lipid Nanoparticle Encapsulating mRNAs Encoding Human OX40L, IL-23, and IL-36γ, for Intratumoral Injection to Patients with Advanced Malignancies: Phase 1 clinical trial NCT02806687. Sponsor: ModernaTX, Inc. (2016–2021). Retrieved from: https://clinicaltrials.gov/study/NCT02806687
  83. Kim, J., Eygeris, Y., Gupta, M., & Sahay, G. (2021). Self-assembled mRNA vaccines. Advanced Drug Delivery Reviews, 170, 83–112. DOI
  84. Knop, K., Hoogenboom, R., Fischer, D., & Schubert, U. S. (2010). Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives. Angewandte Chemie International Edition, 49(36), 6288–6308. DOI
  85. Meng, C., Chen, Z., Li, G., Welte, T., & Shen, H. (2021). Nanoplatforms for mRNA Therapeutics. Advanced Therapeutics, 4(1), 2000099. DOI
  86. Akinc, A., Goldberg, M., Qin, J., Dorkin, J. R., Gamba-Vitalo, C., Maier, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Manoharan, M., Koteliansky, V., Röhl, I., Leshchiner, E. S., Langer, R., & Anderson, D. G. (2009). Development of Lipidoid–siRNA Formulations for Systemic Delivery to the Liver. Molecular Therapy, 17(5), 872–879. DOI
  87. Zhu, X., Tao, W., Liu, D., Wu, J., Guo, Z., Ji, X., Bharwani, Z., Zhao, L., Zhao, X., Farokhzad, O. C., & Shi, J. (2017). Surface De-PEGylation Controls Nanoparticle-Mediated siRNA Delivery In Vitro and In Vivo. Theranostics, 7(7), 1990–2002. DOI
  88. Casper, J., Schenk, S. H., Parhizkar, E., Detampel, P., Dehshahri, A., & Huwyler, J. (2023). Polyethylenimine (PEI) in gene therapy: Current status and clinical applications. Journal of Controlled Release, 362, 667–691. DOI
  89. Teo, S. P. (2022). Review of COVID-19 mRNA Vaccines: BNT162b2 and mRNA-1273. Journal of Pharmacy Practice, 35(6), 947–951. DOI
  90. Csaba, N. S., Sánchez, A., & Alonso, M. J. (2010). Preparation of Poly(Lactic Acid) (PLA) and Poly(Ethylene Oxide) (PEO) Nanoparticles as Carriers for Gene Delivery. Cold Spring Harbor Protocols, 2010(8), pdb. prot5468. DOI
  91. Kim, J.-H., Park, J. S., Yang, H. N., Woo, D. G., Jeon, S. Y., Do, H.-J., Lim, H.-Y., Kim, J. M., & Park, K.-H. (2011). The use of biodegradable PLGA nanoparticles to mediate SOX9 gene delivery in human mesenchymal stem cells (hMSCs) and induce chondrogenesis. Biomaterials, 32(1), 268–278. DOI
  92. Mollé, L. M., Smyth, C. H., Yuen, D., & Johnston, A. P. R. (2022). Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery. WIREs Nanomedicine and Nanobiotechnology, 14(6), e1809. DOI
  93. Chuan, D., Jin, T., Fan, R., Zhou, L., & Guo, G. (2019). Chitosan for gene delivery: Methods for improvement and applications. Advances in Colloid and Interface Science, 268, 25–38. DOI
  94. Germershaus, O., Mao, S., Sitterberg, J., Bakowsky, U., & Thomas Kissel. (2008). Gene delivery using chitosan, trimethyl chitosan or polyethylenglycolgraft- trimethyl chitosan block copolymers: Establishment of structure–activity relationships in vitro. Journal of Controlled Release, 125(2), 145–154. DOI
  95. Mourya, V. K., & Inamdar, N. N. (2009). Trimethyl chitosan and its applications in drug delivery. Journal of Materials Science: Materials in Medicine, 20(5), 1057–1079. DOI
  96. Nikkhoo, A., Rostami, N., Farhadi, S., Esmaily, M., Moghadaszadeh Ardebili, S., Atyabi, F., Baghaei, M., Haghnavaz, N., Yousefi, M., Aliparasti, M. R., Ghalamfarsa, G., Mohammadi, H., Sojoodi, M., & Jadidi-Niaragh, F. (2020). Codelivery of STAT3 siRNA and BV6 by carboxymethyl dextran trimethyl chitosan nanoparticles suppresses cancer cell progression. International Journal of Pharmaceutics, 581, 119236. DOI
  97. Weecharangsan, W., Opanasopit, P., Ngawhirunpat, T., Apirakaramwong, A., Rojanarata, T., Ruktanonchai, U., & Lee, R. J. (2008). Evaluation of chitosan salts as non-viral gene vectors in CHO-K1 cells. International Journal of Pharmaceutics, 348(1–2), 161–168. DOI
  98. Weecharangsan, W., Opanasopit, P., Ngawhirunpat, T., Rojanarata, T., & Apirakaramwong, A. (2006). Chitosan lactate as a nonviral gene delivery vector in COS-1 cells. AAPS PharmSciTech, 7(3), E74–E79. DOI
  99. Rabeea Banoon, S., Mahdi, D. S., Gasaem, N. A., Abed Hussein, Z., & Ghasemian, A. (2024). The Role of Nanoparticles in Gene Therapy: A Review. Journal of Nanostructures, 14(1). DOI
  100. Pelkmans, L., & Helenius, A. (2002). Endocytosis Via Caveolae. Traffic, 3(5), 311–320. DOI
  101. Sabin, J., Alatorre-Meda, M., Miñones, J., Domínguez-Arca, V., & Prieto, G. (2022). New insights on the mechanism of polyethylenimine transfection and their implications on gene therapy and DNA vaccines. Colloids and Surfaces B: Biointerfaces, 210, 112219. DOI