451. Successful Gene Transfer in Passively Immunized Mice With Immunologically-Inert AAVrh.10 Vectors

Abstract

A month after gene transfer, AAVrh.10-i2 (6 out of 6 animals) mutant vectors had considerable transgene expression in the presence of IVIG while gene expression was completely neutralized in all the mice injected with WT-AAVrh.10 vectors. This partial rescue in luciferase expression in the presence of IVIG was ~27 to 64 fold in comparison to WT vector administered animals. To further evaluate their long-term transduction potential, C57BL/6 mice that did not receive IVIG were followed up further. Seventy-two days post vector administration, animals that received AAVrh.10-i2 vector showed a 6.6 fold increase in hepatic luciferase expression when compared to the WT-AAVrh.10 vectors. This was further corroborated by an increase in viral genome copies (2.07 vs. 0.64) in the liver tissue of AAV-rh.10 i2 vector administered mice. Further studies are needed to generate optimal AAVrh.10 vectors with complete immune evasion potential. The development of such AAV vectors with an immunologically-inert phenotype augurs well for their potential use in human gene therapy.