Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success--a personal perspective

Abstract

Fifty years after the discovery of adeno-associated virus (AAV) and more than 30 years after the first gene transfer experiment was conducted, dozens of gene therapy clinical trials are in progress, one vector is approved for use in Europe, and breakthroughs in virus modification and disease modeling are paving the way for a revolution in the treatment of rare diseases, cancer, as well as HIV. This review will provide a historical perspective on the progression of AAV for gene therapy from discovery to the clinic, focusing on contributions from the Samulski lab regarding basic science and cloning of AAV, optimized large-scale production of vectors, preclinical large animal studies and safety data, vector modifications for improved efficacy, and successful clinical applications.

FIG. 1.

Adeno-associated virus serotype 2 atomic structure. The surface topology and electrostatics of AAV2 are shown (modified from Xie et al.). The 25 nm virion capsid shown here is composed of 3 viral proteins, VP1, 2, and 3, and encapsidates an approximately 5 kb ssDNA genome that has been used to encode and deliver transgenes of interest for human gene therapy application.