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adeno-associated virus Sema6A
- Development stage
- Preclinical
- Lead developer
- Fudan University
- Modality
- Gene Therapies
- Administration
- Parenteral
01
Overview
Adeno-associated virus Sema6A (AAV-Sema6A) is an experimental gene therapy designed to treat pulmonary hypertension (PH) by restoring the expression of Semaphorin 6A (Sema6A) in the pulmonary vasculature. Sema6A is a transmembrane protein that, when deficient, leads to endothelial cell apoptosis and pathological vascular remodeling through the disruption of Plexin-A4/VEGFR2 signaling. The therapy utilizes an endothelial cell (EC)-targeting AAV vector to deliver the Sema6A transgene. Preclinical research indicates that AAV-mediated Sema6A overexpression can reduce right ventricular systolic pressure, improve heart function, and attenuate distal vessel muscularization in various rodent models of PH, including Sugen/Hypoxia and monocrotaline-induced models. This approach aims to reverse the step-wise transformation of pulmonary microvascular endothelial cells from an apoptotic phenotype to a hyperproliferative, apoptosis-resistant state.
- Other names
- AAV-Sema6AAAV-Sema-6AAAV-Sema 6AAAV-Sema6A-overexpressing vectorAAV-Sema-6A-overexpressing vectorAAV-Sema 6A-overexpressing vector
02
Targets
OCT (Organic cation transporter family)PLXNA4VEGFR2 (Vascular endothelial growth factor receptor 2)
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