adeno-associated virus Sema6A

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.