Urocortin-2 Gene Transfer for CHF: a Paracrine Approach Using Intravenous AAV8

DESCRIPTION (provided by applicant): Gene transfer for the treatment of cardiovascular diseases is bedeviled by inability to obtain, safely and easily, sufficient cardiac transgene expression. Current methods of gene transfer for heart disease include intramuscular injection into heart muscle or intracoronary delivery, approaches that are cumbersome to apply. Consequently, we have considered the usefulness of a vector encoding a paracrine-type transgene. In this approach, the transgene acts as a hormone, having cardiac effects after being released to the circulation from a distant site. This approach would circumvent the problem of attaining high yield cardiac gene transfer and enable patients to be treated by a systemic injection during an office visit. Furthermore, the approach proposed would eliminate the need for intravenous delivery of therapeutic peptides and thereby circumvent repeated and prolonged hospital stays, high morbidity, and enormous economic costs. The most suited vector to achieve these goa