Gene therapy by editing is an attractive and effective tool to treat monogenic diseases with a few successful entrants into the clinic for diseases such as sickle cell anemia, inherited retinal disorders, etc. However, for diseases that are caused by mutations in specific tissues, the major limitation to using gene editing as targeted therapy is to ensure the effective delivery of the editor to the correct site in the body.

In a new study, scientists from Harvard University established a new muscle-specific gene delivery system. The traditional adeno-associated viral (AAV) vector with therapeutic transgenes worked in the mouse model system to reverse the disease. However, the delivery system failed in humans, and most of the AAVs were going to the liver, which could be toxic at high concentrations.

To improve the homing signal on the AAV-mediated delivery system, the authors identified a family of muscle-tropic capsid variants with a 7-mer peptide with an RGD motif in the hypervariable region and further engineered them to contain a cell type-specific mammalian promoter.