Academic Journal
AAV Vectors in Regenerative Medicine and Cellular Reprogramming: Potential, Pitfalls, and Specificity Constraints.
| Τίτλος: | AAV Vectors in Regenerative Medicine and Cellular Reprogramming: Potential, Pitfalls, and Specificity Constraints. |
|---|---|
| Συγγραφείς: | Abdelnaby M; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), Institutskiy Per., 141701 Dolgoprudny, Russia.; Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 117997 Moscow, Russia., Galiakberova A; Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 117997 Moscow, Russia.; Research Institute of Molecular and Cellular Medicine, RUDN University, 117198 Moscow, Russia., Dashinimaev E; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), Institutskiy Per., 141701 Dolgoprudny, Russia.; Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 117997 Moscow, Russia.; Research Institute of Molecular and Cellular Medicine, RUDN University, 117198 Moscow, Russia.; Medical Institute, Banzarov Buryat State University, 670000 Ulan-Ude, Russia. |
| Πηγή: | International journal of molecular sciences [Int J Mol Sci] 2026 Jul 30; Vol. 27 (15). Date of Electronic Publication: 2026 Jul 30. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| Ιατρικοί όροι (MeSH): | Cellular Reprogramming*/genetics , Regenerative Medicine*/methods , Genetic Vectors*/genetics , Dependovirus*/genetics, Genetic Therapy/methods ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/cytology ; Humans ; Animals ; Gene Transfer Techniques ; Gene Therapy Agents ; Transduction, Genetic |
| Περίληψη: | The adeno-associated virus (AAV) has become the vector of choice for gene therapy and experimental gene delivery, owing to its non-pathogenic nature and ability to achieve persistent gene expression across diverse tissues. AAV has emerged as a key platform in cellular reprogramming and regenerative medicine, with applications spanning transcription factor delivery for in vivo lineage conversion and tissue repair across the CNS, heart, and musculoskeletal systems. However, significant limitations remain, particularly in the context of induced pluripotent stem cell (iPSC) engineering. We assess barriers to efficient iPSC transduction including receptor-dependent entry deficits and activation of p53-dependent DNA damage responses. Although AAV is widely described as non-integrating, evidence indicates that integration events occur in rapidly proliferating and actively reprogramming cells. Critically, we synthesize evidence that cell-type-specific promoters lose fidelity when paired with neurogenic transgene payloads, a cross-tissue problem not addressed in existing AAV reviews, and that published in vivo reprogramming efficiencies may be substantially confounded by promoter leakage in the absence of formal lineage tracing. These aspects, underrepresented in recent platform-level reviews, are specifically emphasized here as a resource for researchers designing rigorous AAV-based reprogramming and gene therapy strategies. |
| References: | J Clin Invest. 2015 Feb;125(2):870-80. (PMID: 25607839) Science. 2009 May 8;324(5928):797-801. (PMID: 19325077) Epigenetics. 2026 Dec;21(1):2606983. (PMID: 41468306) Expert Opin Biol Ther. 2022 Sep;22(9):1067-1071. (PMID: 35373689) Nat Commun. 2025 Mar 10;16(1):2118. (PMID: 40064861) Nat Med. 2007 Apr;13(4):419-22. (PMID: 17369837) Nature. 2007 Jul 19;448(7151):313-7. (PMID: 17554338) Trends Microbiol. 2022 May;30(5):432-451. (PMID: 34711462) Science. 1965 Aug 13;149(3685):754-6. (PMID: 14325163) J Virol. 2001 Aug;75(15):6969-76. (PMID: 11435577) Hum Gene Ther. 2019 Jul;30(7):794-801. (PMID: 30838895) Nat Biomed Eng. 2026 Jun;10(6):1060-1083. (PMID: 42092003) Nat Med. 2019 Mar;25(3):427-432. (PMID: 30778238) Hum Gene Ther. 2008 Dec;19(12):1359-68. (PMID: 18795839) Nat Commun. 2018 Jul 9;9(1):2651. (PMID: 29985406) Nat Biotechnol. 2009 Jan;27(1):59-65. (PMID: 19098898) Mol Ther. 2012 Feb;20(2):329-38. (PMID: 22108859) Mol Ther. 2010 Jun;18(6):1192-9. (PMID: 20407427) Hum Gene Ther. 2020 May;31(9-10):575-589. (PMID: 32000541) Cell Syst. 2022 Jun 15;13(6):499-507.e12. (PMID: 35649419) Mol Ther. 2014 Feb;22(2):338-347. (PMID: 24196577) Front Neurosci. 2017 Mar 29;11:161. (PMID: 28424574) Hum Gene Ther. 2010 Jun;21(6):704-12. (PMID: 20095819) Nat Genet. 1994 Oct;8(2):148-54. (PMID: 7842013) Lancet Neurol. 2023 Dec;22(12):1125-1139. (PMID: 37977713) Cell. 2006 Aug 25;126(4):663-76. (PMID: 16904174) Nat Rev Drug Discov. 2019 May;18(5):358-378. (PMID: 30710128) Stem Cell Reports. 2024 Oct 8;19(10):1389-1398. (PMID: 39241770) Am J Respir Cell Mol Biol. 2023 Sep;69(3):255-265. (PMID: 37315312) Science. 2007 Dec 21;318(5858):1920-3. (PMID: 18063756) Stem Cell Reports. 2021 Sep 14;16(9):2242-2256. (PMID: 34525384) Mol Ther Methods Clin Dev. 2025 Apr 14;33(2):101467. (PMID: 40927767) Nature. 1990 Jan 11;343(6254):180-2. (PMID: 2404210) Science. 2008 Aug 29;321(5893):1218-21. (PMID: 18669821) Nat Biotechnol. 2008 Jan;26(1):101-6. (PMID: 18059259) EBioMedicine. 2023 Apr;90:104531. (PMID: 36947961) Nature. 2007 Jul 19;448(7151):318-24. (PMID: 17554336) Hum Gene Ther. 2022 Jun;33(11-12):579-597. (PMID: 35435735) Nucleic Acids Res. 2015 Feb 18;43(3):1577-92. (PMID: 25605798) Gene Ther. 2011 Jan;18(1):43-52. (PMID: 20703310) Circulation. 2023 Aug;148(5):405-425. (PMID: 37409482) Cell Stem Cell. 2007 Jun 7;1(1):55-70. (PMID: 18371336) Mol Ther Nucleic Acids. 2017 Sep 15;8:13-25. (PMID: 28918015) J Virol. 1998 Feb;72(2):1438-45. (PMID: 9445046) N Engl J Med. 2017 Nov 2;377(18):1713-1722. (PMID: 29091557) Future Virol. 2013 Dec;8(12):1183-1199. (PMID: 24533032) Mol Ther. 2008 Jul;16(7):1189-99. (PMID: 18500252) Nat Commun. 2019 Sep 30;10(1):4439. (PMID: 31570731) Mol Ther Methods Clin Dev. 2023 Aug 18;30:459-473. (PMID: 37674904) Blood. 2013 Jul 4;122(1):23-36. (PMID: 23596044) J Virol. 2008 Mar;82(6):2727-40. (PMID: 18199646) Front Immunol. 2021 May 28;12:660302. (PMID: 34122418) Gene Ther. 2001 Aug;8(16):1248-54. (PMID: 11509958) Skelet Muscle. 2024 May 3;14(1):9. (PMID: 38702726) J Nanobiotechnology. 2025 Mar 24;23(1):242. (PMID: 40128816) Front Cell Dev Biol. 2021 Apr 13;9:662837. (PMID: 33937264) Gene. 2009 Jan 1;428(1-2):20-4. (PMID: 18976699) J Virol. 1989 Sep;63(9):3822-8. (PMID: 2547998) Nat Neurosci. 2017 Aug;20(8):1172-1179. (PMID: 28671695) Front Cell Dev Biol. 2022 Sep 19;10:914386. (PMID: 36200040) Nature. 2009 Dec 3;462(7273):595-601. (PMID: 19898493) Hum Gene Ther. 2018 Mar;29(3):285-298. (PMID: 29378426) Cell. 2021 Sep 16;184(19):4919-4938.e22. (PMID: 34506722) J Embryol Exp Morphol. 1962 Dec;10:622-40. (PMID: 13951335) Hum Gene Ther. 2010 Oct;21(10):1343-8. (PMID: 20497037) J Virol. 2003 Mar;77(6):3495-504. (PMID: 12610125) Mol Ther Methods Clin Dev. 2025 May 21;33(2):101494. (PMID: 40525125) Sci Rep. 2024 Dec 30;14(1):31583. (PMID: 39738170) Neuron. 2012 Jul 26;75(2):283-93. (PMID: 22841313) Mol Ther. 2006 Mar;13(3):528-37. (PMID: 16413228) Mol Ther. 2009 Dec;17(12):2096-102. (PMID: 19672248) Mol Ther Methods Clin Dev. 2020 Jun 01;18:167-175. (PMID: 32637448) Gene Ther. 2022 Jun;29(6):390-397. (PMID: 33753910) J Virol. 2012 Apr;86(8):4463-7. (PMID: 22301147) Int J Mol Sci. 2020 Feb 03;21(3):. (PMID: 32028585) Virol J. 2013 Mar 06;10:74. (PMID: 23497173) Nat Biomed Eng. 2024 Feb;8(2):132-148. (PMID: 37430157) Nat Med. 2020 Jul;26(7):1096-1101. (PMID: 32483358) Adv Sci (Weinh). 2024 Aug;11(29):e2304551. (PMID: 38810137) Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9. (PMID: 11095710) Science. 2007 Jul 27;317(5837):477. (PMID: 17656716) Mol Ther Methods Clin Dev. 2015 Feb 18;2:14067. (PMID: 26052535) Mol Ther. 2022 Dec 7;30(12):3515-3541. (PMID: 36203359) Blood. 2013 Mar 21;121(12):2224-33. (PMID: 23325831) N Engl J Med. 2011 Dec 22;365(25):2357-65. (PMID: 22149959) Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5. (PMID: 2156265) Cell Stem Cell. 2010 Nov 5;7(5):618-30. (PMID: 20888316) Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7038-43. (PMID: 23530235) Front Neurosci. 2014 Feb 26;8:38. (PMID: 24616659) Sci Rep. 2022 May 19;12(1):8356. (PMID: 35589936) Mol Ther Methods Clin Dev. 2025 May 21;33(2):101496. (PMID: 40519324) Cell. 2007 Nov 30;131(5):861-72. (PMID: 18035408) Biol Open. 2021 Sep 15;10(9):. (PMID: 34435198) Science. 2008 Nov 7;322(5903):949-53. (PMID: 18845712) Nat Methods. 2011 May;8(5):409-12. (PMID: 21460823) J Gene Med. 2004 Apr;6(4):395-404. (PMID: 15079814) J Virol. 1983 Feb;45(2):555-64. (PMID: 6300419) Mol Ther. 2013 Mar;21(3):509-19. (PMID: 23358189) J Pediatr. 2020 Oct;225:252-258.e1. (PMID: 32473148) Nature. 2019 May;569(7756):418-422. (PMID: 31068698) Cells. 2024 Aug 23;13(17):. (PMID: 39272980) Nat Commun. 2020 Jun 30;11(1):3279. (PMID: 32606306) BioDrugs. 2017 Aug;31(4):317-334. (PMID: 28669112) Biomaterials. 2014 Aug;35(26):7598-609. (PMID: 24917028) J Clin Invest. 2009 Aug;119(8):2388-98. (PMID: 19587448) Hum Gene Ther. 1996 Nov 10;7(17):2101-12. (PMID: 8934224) Nat Commun. 2025 Apr 18;16(1):3694. (PMID: 40251179) Biotechnol J. 2021 Jan;16(1):e2000025. (PMID: 32975881) PLoS One. 2011;6(11):e27520. (PMID: 22114676) J Gene Med. 2011 Sep;13(9):497-506. (PMID: 22144143) Blood. 2011 Mar 24;117(12):3311-9. (PMID: 21106988) Signal Transduct Target Ther. 2024 Apr 3;9(1):78. (PMID: 38565561) Nucleic Acids Res. 2025 Jan 24;53(3):. (PMID: 39868534) Nat Med. 2006 Mar;12(3):342-7. (PMID: 16474400) Nature. 2010 Feb 25;463(7284):1035-41. (PMID: 20107439) Nat Med. 2002 Mar;8(3):253-61. (PMID: 11875496) |
| Grant Information: | 25-15-00443 Russian Science Foundation |
| Contributed Indexing: | Keywords: adeno-associated virus (AAV); cell-specific targeting; cellular reprogramming; gene therapy; lineage tracing; regenerative medicine |
| Entry Date(s): | Date Created: 20260813 Date Completed: 20260813 Latest Revision: 20260815 |
| Update Code: | 20260815 |
| PubMed Central ID: | PMC13467176 |
| DOI: | 10.3390/ijms27156846 |
| PMID: | 42589500 |
| Βάση Δεδομένων: | MEDLINE |
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