Selective Anti-AAV Antibody Depletion by Hemapheresis and Immunoadsorption

Abstract

One of the greatest barriers for the use of adeno-associated vectors (AAV) in gene therapy is the presence of pre-existing antibodies against AAV in the general population. Since many of the anti-AAV antibodies have the ability to neutralize the transduction target tissues, even patients with low antibody titers must be excluded from clinical trials or therapy. In recent years, various methods have been proposed to overcome this problem, unfortunately with limited success. In this chapter, we describe in detail a protocol for hemapheresis with an immunoadsorption matrix to remove specifically anti-AAV antibodies in an in vivo rat model. Furthermore, this chapter describes in detail the methods to determine the efficiency of hemapheresis and immunoadsorption.