O-26: Somatic gene therapy for hypertension with adeno-associated delivery of antisense to angiotensin type 1 receptor mRNA

Introduction: The goal of gene therapy for hypertension is to produce safe, prolonged reductions of high blood pressure with a single administration of a transgene. We have develeloped gene therapy using adeno-associated virus (AAV) antisense (AS) as a vector because it is safe, stable and effective. To test systemic injection in an adult hypertensive model, this study uses double transgenic (dt) mice, with human renin (hR) and human transgenes. In these mice, plasma Ang II levels are elevated and blood pressure increased (~140-160 mmHg), compared to controls (~100 mmHg). Methods: Therefore, dt mice with established baseline BP of >140-160 mmHg (n=5) were systemically injected (100 μl) with a single dose of 4x1010 infectious particles of rAAV-AT1R-AS. The rAAV contained a CMV promoter and neo1 reporter gene. Control (n=5) received the rAAV vector without AS. Blood pressure recordings by the tailcuff method were made once per week for up to 6 months. Results: One week after injection, BP decreased by 35-50 mmHg (p