Using Empty AAV Capsids to Reduce Inhibitory Effect of Neutralizing Antibodies on AAV Transduction

Jiu Jiang, PhD1, Steven Wright, PhD2, and Ismael Hidalgo, PhD1
1Absorption Systems LLC, 436 Creamery Way, Suite 600, Exton, PA 19341
2Deaprtment of Biology, Carson-Newman University, 1646 Russel Ave, Jefferson City, TN 37760

This poster was presented at AAPS PharmSci 360, 2019

Currently, gene therapy is becoming more promising for treating numerous genetic disorders. The non-pathogenic adeno-associated viruses (AAVs) are among the most frequently used viral vectors for gene therapy. However, patients with pre-existing immunity against AAVs have neutralizing antibodies (NAb) that may hinder viral transduction; thus, they are less likely to benefit from this type of therapy. Since the prevalence of NAb in the human population can reach up to 60%-70% for some serotypes such as AAV2, systematic exclusion of seropositive patients from treatment would greatly limit the potential impact of gene therapy in humans. For this reason, there is a need to understand how NAbs can interact with AAVs and explore strategies to allow expansion in the application of gene therapy in individuals with NAb. The purpose of this study was to investigate, in an in vitro cell-based assay, the potential utility of empty capsids of AAV2 in overcoming the negative effect of NAb on AAV2-mediated transduction.