Gene Therapy Using Adeno-Associated Virus Vectors

Abstract

SUMMARY The unique life cycle of adeno-associated virus (AAV) and its ability to infect both nondividing and dividing cells with persistent expression have made it an attractive vector. An additional attractive feature of the wild-type virus is the lack of apparent pathogenicity. Gene transfer studies using AAV have shown significant progress at the level of animal models; clinical trials have been noteworthy with respect to the safety of AAV vectors. No proven efficacy has been observed, although in some instances, there have been promising observations. In this review, topics in AAV biology are supplemented with a section on AAV clinical trials with emphasis on the need for a deeper understanding of AAV biology and the development of efficient AAV vectors. In addition, several novel approaches and recent findings that promise to expand AAV's utility are discussed, especially in the context of combining gene therapy ex vivo with new advances in stem or progenitor cell biology.

Nano-sized carriers in gene therapy for renal fibrosisin vivo

“…The exogenous genes delivered using adenoviral vectors do not integrate into the host genome and do not replicate during cell division, resulting in short periods of gene expression of the targeted cells [55]. To overcome this drawback of the adenoviral vector, AAV vectors have been developed [58]. AAV vectors are single-stranded, non-enveloped DNA viral vectors, 18–26 nm in diameter, with a genome of 4–5 kb [56,58,59].…”

“…To overcome this drawback of the adenoviral vector, AAV vectors have been developed [58]. AAV vectors are single-stranded, non-enveloped DNA viral vectors, 18–26 nm in diameter, with a genome of 4–5 kb [56,58,59]. AAV vectors can also transfect genes into both dividing and non-dividing cells, and may incorporate genes into the host genome.…”

“…AAV vectors can also transfect genes into both dividing and non-dividing cells, and may incorporate genes into the host genome. Therefore, the duration of gene expression delivered using AAV vectors is considered to be longer compared with that delivered by adenoviral vectors [58]. AAV vectors were shown to have a low immunogenicity compared with adenoviral vectors [58].…”

“…Therefore, the duration of gene expression delivered using AAV vectors is considered to be longer compared with that delivered by adenoviral vectors [58]. AAV vectors were shown to have a low immunogenicity compared with adenoviral vectors [58]. AAV vectors serotype 9, designed for expression of hepatocyte growth factor (HGF), which is an anti-fibrotic cytokine, showed remarkable attenuation of tubulointerstitial fibrosis in a mouse model of renal fibrosis [40].…”

Nano-sized carriers in gene therapy for peritoneal fibrosisin vivo

“…AAVs are single-stranded, non-enveloped DNA viral vectors 18–26 nm in diameter, with a genome of 4–5 kb [46,48,49]. AAVs can deliver transgenes into both dividing and non-dividing cells, and can incorporate their transgenes into the host genome [46,48,49].…”