Preprint
Common AAV gene therapy vectors show indiscriminate transduction of living human brain cell types
bioRxiv
Cold Spring Harbor Laboratory Press
11/15/2024
DOI: 10.1101/2024.11.14.623624
PMCID: PMC11601464
PMID: 39605617
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 ex vivo 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.Competing Interest StatementThe authors have declared no competing interest.
Details
- Title: Subtitle
- Common AAV gene therapy vectors show indiscriminate transduction of living human brain cell types
- Creators
- Jp McginnisJoshua Ortiz-Guzman - Baylor College of MedicineMaria Guevara - Baylor College of MedicineSai Mallannagari - Baylor College of MedicineBenjamin Belfort - Baylor College of MedicineSuyang Bao - Baylor College of MedicineSnighda SrivastavaMaria Morkas - Baylor College of MedicineEmily Ji - Baylor College of MedicineAngela Addison - Baylor College of MedicineEvelyne Tantry - Baylor College of MedicineSarah Chen - Baylor College of MedicineYing WangZihong ChenKalman Katlowitz - Baylor College of MedicineJeffrey Lange - Stowers Institute for Medical ResearchMelissa Blessing - Baylor College of MedicineCarrie Mohila - Baylor College of MedicineM LjungbergGuillermo Aldave - Baylor College of MedicineAli Jalali - Baylor College of MedicineAkash Patel - Baylor College of MedicineSameer Sheth - Baylor College of MedicineHoward Weiner - Baylor College of MedicineShankar Gopinath - Baylor College of MedicineGanesh Rao - Baylor College of MedicineAkdes Serin-HarmanciDaniel Curry - Baylor College of MedicineBenjamin Arenkiel - Baylor College of Medicine
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- DOI
- 10.1101/2024.11.14.623624
- PMID
- 39605617
- PMCID
- PMC11601464
- NLM abbreviation
- bioRxiv
- ISSN
- 2692-8205
- eISSN
- 2692-8205
- Publisher
- Cold Spring Harbor Laboratory Press; Cold Spring Harbor
- Language
- English
- Date posted
- 11/15/2024
- Academic Unit
- Pathology
- Record Identifier
- 9984757157602771
Metrics
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