The influence of murine genetic background in AAV transduction of the mouse brain.

Abstract

Adeno-associated virus (AAV) vectors have become an important tool for delivering therapeutic genes for a wide range of neurological diseases. AAV serotypes possess differential cellular tropism in the central nervous system. Although several AAV serotypes or mutants have been reported to transduce the brain efficiently, conflicting data occurs across studies with the use of various rodent strains from different genetic backgrounds. Herein, we performed a systematic comparison of brain transduction properties among five AAV serotypes (AAV2, 5, 7, 8, and 9) in two common rodent strains (C57BL/6J and FVB/N), following local intra-striatal injection of AAV vectors encoding EGFP driven by the CBh promoter. Important differences were found regarding overall transduction efficiency, cellular tropism, and retrograde axonal transport among the AAV serotypes and between the mouse strains. We have further found loss of NeuN-immunoreactivity and microglia activation from AAV transduction in the different mouse strains. The important strain-specific differences from our study suggest that the genetic background of the mouse strains may affect AAV serotype transduction properties in the brain. This data can provide valuable information about how to choose an effective AAV vector for clinical application and interpret the data obtained from preclinical studies and clinical trials.