Nature Biotechnology pp 321 - 328

In a head-to-head comparison of several gene therapy delivery approaches, researchers have identified the optimal means of delivering therapeutic genes to muscle tissues with a single intravenous injection — an approach that may prove useful for treating heart disease and muscular dystrophies.

In the March issue of Nature Biotechnology, Xiao Xiao and colleagues identify a virus that overcomes the obstacle of delivering genes across the blood vessel barrier to heart and skeletal muscles in animals. A comparative study of many different types of modified adeno-associated virus (AAV) revealed a subtype - AAV8, particularly adept at delivering genes to the skeletal and cardiac muscles of mice and hamsters. Previous attempts to systemically deliver genes into animals using AAV required the use of drugs to help them cross the blood vessel walls and gain access to muscle. One subtype, AAV8, however, proved to be particularly effective on its own.

To validate their findings, the authors then used AAV8 to deliver a repaired version of the delta-sarcoglycan gene into hamsters with a gene defect associated with a type of muscular dystrophy and heart failure. They show that AAV8 was able to deliver the delta-sarcoglycan gene to the hamsters' tissues, resulting in the correction of pathological signs of dystrophic heart and skeletal muscles.