National Institute of General Medical Sciences 5R35GM122564-08

Adeno-Associated Virus Gene Therapy Vectors: Molecular Interactions on Cell Entry

This award funds research to improve the efficiency and safety of adeno-associated virus gene therapy vectors by studying their molecular interactions during cell entry, aiming to reduce immunotoxicity and enhance treatment outcomes.

Description

Adeno-associated virus (AAV) is a leading delivery vector for gene therapies for a wide range of genetic diseases. Recent FDA approvals and ongoing clinical trials highlight its importance. Challenges include inefficient transduction requiring high doses, risking immunotoxicity. The project aims to understand AAV’s host interactions at a molecular level, focusing on key receptors like AAVR and GPR108, using cryo-EM and cryo-electron tomography. It will also reevaluate antibody neutralization mechanisms and develop computational methods to improve cryo-EM structure resolution. The goal is to enhance vector efficiency and safety for gene therapy applications.

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