Ultrasound-guided left heart injection: a safer and more efficient strategy for mouse thoracic aortic gene delivery

Abstract Thoracic aortic disease poses a significant threat due to its high mortality rates and genetic underpinnings. While gene therapy holds promise for cures, the challenge lies in achieving effective and safe gene delivery to the thoracic aorta. Tail vein injection (TI), is hindered by off-target effects and hepatotoxicity, and traditional blinded percutaneous left heart injection (TLI) carries a heightened risk of bleeding and mortality. To address these limitations, ultrasound-guided techniques present a viable solution. Adeno-associated virus (AAV) vectors were delivered into the thoracic aorta of mice through TI, TLI, and ultrasound-guided percutaneous left heart injection(ULI).While all three injection methods can achieve gene transfection in the thoracic aorta, the ULI approach provides the optimal balance between high transduction efficiency and safety. The ULI method represents an efficient and safe strategy for targeted gene delivery to the mouse thoracic aorta, providing a powerful tool for preclinical aortic gene therapy research that warrants broader application.