Aptamer engineering of lentiviral vectors for cardiac gene therapies

PROJECT SUMMARY/ABSTRACT Overview: Hypertrophic cardiomyopathy is the leading cause of sudden death in young individuals, where several loss-of-function mutations in key sarcomeric proteins cause hypertrophy. Gene therapy approaches that drive the overexpression of the correct genes can be used to remodel the heart tissue and restore function. However, no gene therapies have been developed for in vivo targeting of the heart to date. A key bottleneck in the field is the ability to engineer advanced viral vectors with prescribed tropism in the patient’s body. Lentiviral vector (LVV) engineering applies rational design principles to define components of the vector envelope, such as attachment proteins, leading to vectors with programmable tissue specificity and off-target activity.