Adeno-Associated Virus (AAV) As a Vector for Gene Therapy

Overview

Journal BioDrugs

Specialties Allergy & Immunology
Genetics
Pharmacology

Date 2017 Jul 3

PMID 28669112

Citations 517

Authors

Michael F Naso

Brian Tomkowicz

William L Perry 3rd

William R Strohl

Affiliations

Soon will be listed here.

Abstract

There has been a resurgence in gene therapy efforts that is partly fueled by the identification and understanding of new gene delivery vectors. Adeno-associated virus (AAV) is a non-enveloped virus that can be engineered to deliver DNA to target cells, and has attracted a significant amount of attention in the field, especially in clinical-stage experimental therapeutic strategies. The ability to generate recombinant AAV particles lacking any viral genes and containing DNA sequences of interest for various therapeutic applications has thus far proven to be one of the safest strategies for gene therapies. This review will provide an overview of some important factors to consider in the use of AAV as a vector for gene therapy.

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References

Plotkin J, Robins H, Levine A . Tissue-specific codon usage and the expression of human genes. Proc Natl Acad Sci U S A. 2004; 101(34):12588-91. PMC: 515101. DOI: 10.1073/pnas.0404957101. View

Greenberg B, Butler J, Felker G, Ponikowski P, Voors A, Desai A . Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet. 2016; 387(10024):1178-86. DOI: 10.1016/S0140-6736(16)00082-9. View

Dong B, Nakai H, Xiao W . Characterization of genome integrity for oversized recombinant AAV vector. Mol Ther. 2009; 18(1):87-92. PMC: 2803017. DOI: 10.1038/mt.2009.258. View

Maersch S, Huber A, Buning H, Hallek M, Perabo L . Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology. 2009; 397(1):167-75. DOI: 10.1016/j.virol.2009.10.021. View

Hadri L, Kratlian R, Benard L, Maron B, Dorfmuller P, Ladage D . Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension. Circulation. 2013; 128(5):512-23. PMC: 3908449. DOI: 10.1161/CIRCULATIONAHA.113.001585. View

Nam H, Lane M, Padron E, Gurda B, McKenna R, Kohlbrenner E . Structure of adeno-associated virus serotype 8, a gene therapy vector. J Virol. 2007; 81(22):12260-71. PMC: 2168965. DOI: 10.1128/JVI.01304-07. View

Dalkara D, Byrne L, Klimczak R, Visel M, Yin L, Merigan W . In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous. Sci Transl Med. 2013; 5(189):189ra76. DOI: 10.1126/scitranslmed.3005708. View

Wang B, Li J, Fu F, Chen C, Zhu X, Zhou L . Construction and analysis of compact muscle-specific promoters for AAV vectors. Gene Ther. 2008; 15(22):1489-99. DOI: 10.1038/gt.2008.104. View

Fish K, Ishikawa K . Advances in gene therapy for heart failure. Discov Med. 2015; 19(105):285-91. View

10.

Uhrig S, Coutelle O, Wiehe T, Perabo L, Hallek M, Buning H . Successful target cell transduction of capsid-engineered rAAV vectors requires clathrin-dependent endocytosis. Gene Ther. 2011; 19(2):210-8. DOI: 10.1038/gt.2011.78. View

11.

Bish L, Morine K, Sleeper M, Sanmiguel J, Wu D, Gao G . Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat. Hum Gene Ther. 2008; 19(12):1359-68. PMC: 2940566. DOI: 10.1089/hum.2008.123. View

12.

DiMattia M, Nam H, Van Vliet K, Mitchell M, Bennett A, Gurda B . Structural insight into the unique properties of adeno-associated virus serotype 9. J Virol. 2012; 86(12):6947-58. PMC: 3393551. DOI: 10.1128/JVI.07232-11. View

13.

Bartel M, Weinstein J, Schaffer D . Directed evolution of novel adeno-associated viruses for therapeutic gene delivery. Gene Ther. 2012; 19(6):694-700. DOI: 10.1038/gt.2012.20. View

14.

Selkoe D, Hardy J . The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016; 8(6):595-608. PMC: 4888851. DOI: 10.15252/emmm.201606210. View

15.

Summerford C, Samulski R . Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol. 1998; 72(2):1438-45. PMC: 124624. DOI: 10.1128/JVI.72.2.1438-1445.1998. View

16.

Aslanidi G, Lamb K, Zolotukhin S . An inducible system for highly efficient production of recombinant adeno-associated virus (rAAV) vectors in insect Sf9 cells. Proc Natl Acad Sci U S A. 2009; 106(13):5059-64. PMC: 2654393. DOI: 10.1073/pnas.0810614106. View

17.

Chandler R, Sands M, Venditti C . Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models. Hum Gene Ther. 2017; 28(4):314-322. PMC: 5399742. DOI: 10.1089/hum.2017.009. View

18.

Greenberg B, Butler J, Felker G, Ponikowski P, Voors A, Pogoda J . Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure. Gene Ther. 2015; 23(3):313-9. PMC: 6558655. DOI: 10.1038/gt.2015.109. View

19.

Batchu R, Shammas M, Wang J, Munshi N . Interaction of adeno-associated virus Rep78 with p53: implications in growth inhibition. Cancer Res. 1999; 59(15):3592-5. View

20.

Murillo O, Luqui D, Gazquez C, Martinez-Espartosa D, Navarro-Blasco I, Monreal J . Long-term metabolic correction of Wilson's disease in a murine model by gene therapy. J Hepatol. 2015; 64(2):419-426. DOI: 10.1016/j.jhep.2015.09.014. View