Utility of a Recombinant Adeno-Associated Viral Vector Reference Standard

by Terence R. Flotte, Parris Burd, and Richard O. Snyder, PhD
Volume 1, Issue 3 (Fall 2002)

Recombinant adeno-associated viral (rAAV) vectors are known to be efficient vehicles for gene transfer in animal models. The attractive feature of this vector system consists primarily of long-term gene expression with little or no associated toxicities following administration to a variety of tissues. Previous and ongoing clinical trials in humans demonstrate a very good overall safety profile, but problems persist due to the lack of any systematic method for normalizing doses administered to animals and humans. To date, most of the work involves AAV serotype 2 vectors, but vector systems based on other AAV serotypes continue to develop rapidly. Administered doses are usually based on titer, but the defective nature of AAV makes determining vector infectious units difficult. Titering methods based on vector genomes (using hybridization, real-time PCR, or spectrophotometry) are more reliable, but give no information as to the infectivity of the vector. Determining infectious titer is critical, as the ratio of infectious virions to vector genome-containing virions helps to determine the dose, potency, and strength of the vector preparation…

Flotte TR, Burd P, Snyder RO. Utility of a Recombinant Adeno-Associated Viral Vector Reference Standard. BioProcess J, 2002; 1(3): 75-77.