Common AAV Gene Therapy Vectors Show Indiscriminate Transduction of Living Human Brain Cell Types

Overview

Journal bioRxiv

Date 2024 Nov 28

PMID 39605617

Authors

J P McGinnis

Joshua Ortiz-Guzman

Maria Camila Guevara

Sai Mallannagari

Benjamin D W Belfort

Suyang Bao

Snigdha Srivastava

Maria Morkas

Emily Ji

Angela Addison

Evelyne K Tantry

Sarah Chen

Ying Wang

Zihong Chen

Kalman A Katlowitz

Jeffrey J Lange

Melissa M Blessing

Carrie A Mohila

M Cecilia Ljungberg

Guillermo Aldave

Ali Jalali

Akash Patel

Sameer A Sheth

Howard L Weiner

Shankar Gopinath

Ganesh Rao

Akdes Serin Harmanci

Daniel Curry

Benjamin R Arenkiel

Affiliations

Soon will be listed here.

Abstract

The development of cell-type-specific gene therapy vectors for treating neurological diseases holds great promise, but has relied on animal models with limited translational utility. We have adapted an organotypic model to evaluate adeno-associated virus (AAV) transduction properties in living slices of human brain tissue. Using fluorescent reporter expression and single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.

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