A High-Efficiency AAV for Endothelial Cell Transduction Throughout the Central Nervous System

Area of Science:

• Neuroscience
• Vascular Biology
• Gene Therapy

Background:

• Endothelial cells are vital for nervous system function.
• Endothelial dysfunction is implicated in numerous neurological diseases.
• Limited tools exist for *in vivo* genetic interrogation of endothelial cells in the central nervous system (CNS).

Purpose of the Study:

• To develop and characterize a novel adeno-associated virus (AAV) vector for specific and efficient transduction of CNS endothelial cells.
• To assess the vector's efficacy across different CNS vasculature and species.
• To demonstrate the vector's utility for genetic manipulation in endothelial cells.

Main Methods:

• Development of a novel AAV capsid, termed AAV-BI30.
• Systemic administration of AAV-BI30 in adult C57BL/6 mice.
• Evaluation of transduction efficiency in brain, retina, and spinal cord vasculature.
• Testing in various mouse strains, rats (*in vivo*), and human brain microvascular endothelial cells (*in vitro*).
• Demonstration of Cre-mediated gene manipulation.

Main Results:

• AAV-BI30 specifically and efficiently transduces arterial, capillary, and venous endothelial cells throughout the CNS at low systemic doses.
• Robust transduction observed across multiple mouse strains, rats, and human endothelial cells.
• Efficient and endothelial-specific Cre-mediated gene manipulation was achieved in the CNS.

Conclusions:

• AAV-BI30 is a powerful new tool for targeting CNS endothelial cells.
• It facilitates research in neurovascular biology and the study of endothelial dysfunction in neurological diseases.
• This vector holds promise for developing novel therapeutics for CNS disorders.