Indu Rajapaksha

By Indu Rajapaksha, Peter Angus and Chandana Herath

Gene therapy is a novel promising approach for treating a spectrum of inherited and non-inherited disorders by delivering therapeutic genes to specific organs or tissues. Of the viral vectors that have been used to date to deliver the genes of interest, the adeno-associated viral (AAV) vector appears to be the most safe and effective vehicle and has the ability to maintain long-term gene and protein expression following a single injection of the vector. Gene therapy studies using AAV vector have shown significant progress not only in animal models but also in human gene therapy with no known pathogenicity. While success has been achieved in gene therapy using AAV vector to deliver the target genes for inherited disorders, however, clinical trials are yet to begin to see whether gene therapy has promise for treatment of non-inherited diseases. This chapter describes AAV biology, viral structure, and cell entry mechanisms, with special emphasis on AAV tissue tropism achieved by manipulating different serotypes and capsid engineering. This chapter also discusses successful application of the AAV vector for non-inherited disorders in animal models with particular reference to liver fibrosis, outlining advantages, disadvantages, and future challenges that this therapy may face.

Part of the book: In Vivo and Ex Vivo Gene Therapy for Inherited and Non-Inherited Disorders