{"id":214217,"date":"2025-05-17T17:08:41","date_gmt":"2025-05-17T22:08:41","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2025\/05\/emerging-non-viral-vectors-for-gene-delivery"},"modified":"2025-05-17T17:08:41","modified_gmt":"2025-05-17T22:08:41","slug":"emerging-non-viral-vectors-for-gene-delivery","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2025\/05\/emerging-non-viral-vectors-for-gene-delivery","title":{"rendered":"Emerging non-viral vectors for gene delivery"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/emerging-non-viral-vectors-for-gene-delivery3.jpg\"><\/a><\/p>\n<p>The development of COVID-19 vaccines has sparked widespread interest. mRNA-based therapies are rapidly gaining attention owing to their unique advantages in quickly developing vaccines and immunotherapy for various ailments [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\" title=\"Hajj KA, Whitehead KA. Tools for translation: non-viral materials for therapeutic mRNA delivery. Nat Rev Mater. 2017;2:17056.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR1\" id=\"ref-link-section-d159071863e568\">1<\/a>, <a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\" title=\"Kowalski PS, Rudra A, Miao L, Anderson DG. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol Ther. 2019;27:710&ndash;28.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR2\" id=\"ref-link-section-d159071863e571\">2<\/a>]. Given that most human diseases stem from genetic factors, gene therapy represents a promising modality for addressing various inherited or acquired disorders by replacing faulty genes or silencing genes [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 3\" title=\"Weiss C, Carriere M, Fusco L, Capua I, Regla-Nava JA, Pasquali M, Scott AA, Vitale F, Unal MA, Mattevi C, et al. Toward nanotechnology-enabled approaches against the COVID-19 pandemic. ACS Nano. 2020;14:6383&ndash;406.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR3\" id=\"ref-link-section-d159071863e574\">3<\/a>]. Gene therapy encompasses the targeted exploitation of genetic material, which includes gene replacement through DNA or mRNA [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\" title=\"Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15:541&ndash;55.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR4\" id=\"ref-link-section-d159071863e577\">4<\/a>, <a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\" title=\"Yin H, Kauffman KJ, Anderson DG. Delivery technologies for genome editing. Nat Rev Drug Discov. 2017;16:387&ndash;99.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR5\" id=\"ref-link-section-d159071863e580\">5<\/a>]; gene silencing utilizing siRNA or miRNA [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 6\" title=\"Lostale-Seijo I, Montenegro J. Synthetic materials at the forefront of gene delivery. Nat Rev Chem. 2018;2:258&ndash;77.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR6\" id=\"ref-link-section-d159071863e584\">6<\/a>], and CRISPR-Cas9 based gene editing [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\" title=\"Liu S, Cheng Q, Wei T, Yu X, Johnson LT, Farbiak L, Siegwart DJ. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing. Nat Mater. 2021;20:701&ndash;10.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR7\" id=\"ref-link-section-d159071863e587\">7<\/a>].<\/p>\n<p>However, achieving safe and efficient gene delivery to specific cells requires overcoming multiple biological barriers, including extracellular obstacles such as enzyme degradation, serum protein interactions, electrostatic repulsion of genes and cell membranes, and innate immune system, as well as intracellular obstacles such as endosomal escape, transport barriers, precise release [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 8\" title=\"Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y. Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv Drug Deliver Rev. 2015;81:142&ndash;60.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR8\" id=\"ref-link-section-d159071863e593\">8<\/a>]. Therefore, gene vectors require several characteristics such as high gene condensation; favorable serum stability to avoid non-specific serum protein interactions, endonuclease degradation, and renal clearance; achieved specific targeting cell or tissues; effective transport into the cytoplasm thereby facilitating gene transfection (mRNA, siRNA and miRNA); precise gene release and scheduling, and nuclear localization that enables DNA transcription. Comprehensive exploration of transfection mechanisms can aid in the development of high-performance gene vectors [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\" title=\"Pack DW, Hoffman AS, Pun S, Stayton PS. Design and development of polymers for gene delivery. Nat Rev Drug Discov. 2005;4:581&ndash;93.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR9\" id=\"ref-link-section-d159071863e596\">9<\/a>, <a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\" title=\"Guo X, Huang L. Recent advances in nonviral vectors for gene delivery. Acc Chem Res. 2012;45:971&ndash;9.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR10\" id=\"ref-link-section-d159071863e599\">10<\/a>].<\/p>\n<p>Gene vectors generally include viral vectors and non-viral vectors. Presently, approximately 70% of clinical gene therapy trials employ viral vectors, which include retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses. Due to their exceptional infectivity, virus-based vectors typically exhibit excellent gene transfection capabilities. However, the clinical safety of viral vectors has been questioned due to their propensity to stimulate immunogenic reactions and induce transgene insertion mutations. Moreover, viral vectors possess several limitations, including low gene loading capacity, inability to deliver large-sized genes, complicated preparation procedures, and the patient cannot be repeatedly administered [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\" title=\"Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15:541&ndash;55.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR4\" id=\"ref-link-section-d159071863e605\">4<\/a>]. In contrast, non-viral vectors, particularly lipid nanoparticles (LNPs) and cationic polymers, have demonstrated robust gene loading capacity, heigh safety and practicability, simplicity preparation [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\" title=\"Guo X, Huang L. Recent advances in nonviral vectors for gene delivery. Acc Chem Res. 2012;45:971&ndash;9.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR10\" id=\"ref-link-section-d159071863e608\">10<\/a>, <a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\" title=\"Patil S, Gao Y-G, Lin X, Li Y, Dang K, Tian Y, Zhang W-J, Jiang S-F, Qadir A, Qian A-R. The development of functional non-viral vectors for gene delivery. Int J Mol Sci. 2019;20:5491.\" href=\"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-023-02044-5#ref-CR11\" id=\"ref-link-section-d159071863e611\">11<\/a>]. Consequently, non-viral vectors are exhibiting tremendous potential for further clinical development and application. Our review primarily highlights the significant potential of non-viral vectors, particularly lipid nanoparticles (LNPs), highly branched poly(\u03b2-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). We intend to provide a detailed examination of the latest research progress and existing limitations of non-viral gene vectors over recent years.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The development of COVID-19 vaccines has sparked widespread interest. mRNA-based therapies are rapidly gaining attention owing to their unique advantages in quickly developing vaccines and immunotherapy for various ailments [1, 2]. Given that most human diseases stem from genetic factors, gene therapy represents a promising modality for addressing various inherited or acquired disorders by replacing [\u2026]<\/p>\n","protected":false},"author":661,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1902,11,412,4],"tags":[],"class_list":["post-214217","post","type-post","status-publish","format-standard","hentry","category-bioengineering","category-biotech-medical","category-genetics","category-nanotechnology"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/214217","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/661"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=214217"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/214217\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=214217"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=214217"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=214217"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}