Assessment of AAV9 Distribution and Transduction in Rats After Administration Through Intrastriatal, Intracisterna Magna and Lumbar Intrathecal Routes

Overview

Journal Gene Ther

Date 2022 May 31

PMID 35637286

Authors

Jayanth Chandran

Ekram Ahmed Chowdhury

Michael Perkinton

Tanguy Jamier

Daniel Sutton

Shengjia Wu

Claire Dobson

Dhaval K Shah

Iain Chessell

Guy M L Meno-Tetang

Affiliations

Soon will be listed here.

Abstract

Challenges in obtaining efficient transduction of brain and spinal cord following systemic AAV delivery have led to alternative administration routes being used in clinical trials that directly infuse the virus into the CNS. However, data comparing different direct AAV injections into the brain remain limited making it difficult to choose optimal routes. Here we tested both AAV9-egfp and AAV9-fLuc delivery via intrastriatal (IST), intracisterna magna (ICM) and lumbar intrathecal (LIT) routes in adult rats and assessed vector distribution and transduction in brain, spinal cord and peripheral tissues. We find that IST infusion leads to robust transgene expression in the striatum, thalamus and cortex with lower peripheral tissue transduction and anti-AAV9 capsid titers compared to ICM or LIT. ICM delivery provided strong GFP and luciferase expression across more brain regions than the other routes and similar expression in the spinal cord to LIT injections, which itself largely failed to transduce the rat brain. Our data highlight the strengths and weaknesses of each direct CNS delivery route which will help with future clinical targeting.

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