Dual Vector Expansion of the Recombinant AAV Packaging Capacity
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Adeno-associated virus (AAV) as a vector for gene therapy of cardiovascular diseases has received much recent attention (1 –6 ). This enthusiasm is based on the success of numerous proof of principal gene transfer experiments. Stable high-level expression has been achieved following a variety of delivery methods (direct cardiac muscle injection, coronary vascular or carotid artery infection) and in a wide range of animal models from rodents to pigs (7 –12 ). A side-by-side comparison between viral and nonviral vectors in rabbit heart suggests that rAAV is much more efficient than nonviral vectors such as naked or liposome-complexed DNA. At the same time, rAAV also displays the least inflammatory response in comparison with other viral vectors such as adenovirus and herpes simplex virus (13 ). Regulated myocardial transgene expression has also been demonstrated with an AAV vector containing glucocorticoid response elements in rat heart (14 ).