Adeno-associated virus and the development of adeno-associated virus vectors: a historical perspective

Adeno-associated virus (AAV) was discovered almost 40 years ago 1–3 and the first AAV vectors were described 20 years ago 4–6, which led to initiation of the first human clinical trial of an AAV vector some 8 years ago, in cystic fibrosis patients 7. These events also delineate three periods in the history of AAV vector development. In the first 20 years, the basic elements of the AAV genome structure, growth cycle, and latency were described. In the early 1980s, infectious molecular clones of AAV serotype 2 were generated and the AAV2 DNA sequence was determined.