AAV5-CMV-iCre

The success of gene therapy relies on an efficient method to transfer functional genes into cells to correct dysfunctional endogenous genes. Over the past three decades, recombinant viral vectors, such as those derived from adenovirus, retrovirus, and lentivirus, have become highly efficient gene delivery vehicles, although safety issues have been a concern. Vectors derived from adeno-associated virus (AAV) have become increasingly popular as delivery systems for therapeutic gene transfer, primarily due to their lack of pathogenicity and broad tropism.

Originally discovered as a contaminant in simian adenovirus preparations, AAV is a nonenveloped, single-stranded DNA virus with a small icosahedral capsid of approximately 25 nanometers. It is classified as a member of the Parvoviridae family but is easily distinguished from other family members by its inability to replicate in the absence of a helper virus, such as adenovirus or herpes simplex virus. To date, 13 naturally occurring AAV serotypes of human and simian origin have been described and evaluated for in vivo transduction (AAV1-13). They exhibit broad tissue transduction preferences and generally show low immunogenicity and sustained transgene expression. Combined with their safety profile, AAV vectors have been used with remarkable success in early and late-stage clinical trials for monogenic diseases such as hemophilia, Leber's congenital blindness, and muscular dystrophy.