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Updated: Feb 10, 2026
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Widespread Transduction of Mouse Neocortical Neurons by Subarachnoid Injection of AAV2
Published on: May 23, 2025
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Rationally designed AAV2 and AAVrh8R capsids provide improved transduction in the retina and brain
Jennifer A Sullivan1, Lisa M Stanek2, Michael J Lukason2
1Sanofi, 49 New York Avenue, Framingham, MA, 01701-9322, USA. Jennifer.Sullivan@sanofi.com.
Gene Therapy
|May 23, 2018
Summary
Engineered adeno-associated virus (AAV) capsids show improved gene delivery to the retina and brain. These modified vectors offer enhanced transduction for potential gene therapy applications.
Area of Science:
- Gene Therapy
- Molecular Biology
- Virology
Background:
- Adeno-associated virus (AAV) vectors are crucial for gene therapy, but efficient delivery to target organs remains a challenge.
- Optimizing AAV capsid properties is essential for successful therapeutic applications.
Purpose of the Study:
- To engineer adeno-associated virus (AAV) serotype 2 (AAV2) and AAVrh8R capsids for enhanced gene delivery to the retina and brain.
- To investigate how capsid modifications affecting receptor binding and surface charge influence transduction efficiency.
Main Methods:
- Rational design approach to modify AAV2 and AAVrh8R capsid proteins.
- Introduction of mutations (e.g., R585A, R588A) in AAV2 to disrupt heparan sulfate proteoglycan binding (AAV2-HBKO).
- Alteration of surface charge on AAVrh8R by modifying arginine residues.
Main Results:
- AAV2-HBKO showed reduced intravitreal transduction but enhanced subretinal photoreceptor transduction in mice compared to wild-type AAV2.
- Intrastriatal delivery of AAV2-HBKO resulted in broader striatal and cortical gene expression than parental AAV2.
- Modifying arginine residues on the AAVrh8R capsid significantly impacted subretinal transduction efficiency.
Conclusions:
- Capsid engineering is a viable strategy to improve AAV vector tropism and transduction efficiency for gene therapy.
- Specific capsid modifications can enhance gene delivery to distinct neural tissues like the retina and brain.
- These findings support the development of optimized AAV vectors for clinical gene therapy applications.
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