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AAV9 mediates more specific cardiac gene transfer in the rat than AAV2, AAV5, AAV7, and AAV8

Cardiac gene transfer may serve as a novel therapeutic approach for heart disease in the USA. Numerous serotypes of AAV have been identified with variable tropisms to cardiac tissue. In vitro and in vivo experiments were undertaken to compare cardiac tropisms of AAV‐2, 5, 7, 8, and 9. For the in vitro study, 107 genome copies (gc) of AAV‐2, 5, 7, 8, or 9, expressing GFP under the CBA promoter, transfected both rat neonatal cardiac myocytes (RNCM) and fibroblasts (RNCF). 3 days post viral transduction, GFP expression was visualized under a microscope. In vitro results indicated that AAV9 and AAV2 showed the highest transducing efficiency in RNCM. Only AAV2 produced any transduction in the RNCF, which was minimal. In the in vivo studies, 5‐day‐old rats were intra‐cardiacly injected with 4x1010 gc of either AAV‐2, 5, 7, 8, or 9. 1 and 2 months post gene delivery, rats were killed and tissues (heart, liver, lung, and kidney) were collected. GFP distribution was visualization using the microscope. The level of GFP gene expression was also measured by Real‐Time PCR. In vivo results indicated that transduction efficiency order in the heart was: AAV9>AAV8>AAV7>>>>AAV2=AAV5. The transduction efficiency order in the liver was: AAV2>AAV5>AAV7>AAV8>AAV9. No to minimal expression was found in the lung and kidney for all serotypes. Collectively these results suggest that AAV9 provides the best transduction efficiency in cardiac tissue.