These recombinant adeno-associated virus (rAAV) capsids enable improved targeting of gene therapy to striated muscle while minimizing delivery to the liver. Duchenne Muscle Disorder (DMD) is a rare genetic disorder involving progressive muscle weakness and degradation due to the defective expression of the dystrophin protein. DMD patients experience initial dystrophy of external muscles, with an eventual impairment of heart and pulmonary function, resulting in a 100 percent fatality rate and a median life expectancy of approximately 28 years. rAAVs have emerged as vectors for the delivery of gene therapy in a number of different diseases, including DMD. However, the majority of delivery strategies involve systemic administration, reducing drug specificity and necessitating high doses, triggering several undesirable immune responses and serious adverse effects.
Researchers at the University of Florida have redesigned rAAV capsid proteins for the targeted delivery of gene therapy to striated muscles while minimizing delivery to the liver. By providing increased tissue-specificity, it enables a reduction in necessary doses, achieving higher efficacy, and reducing costs and safety concerns.
Targeted delivery of gene therapy to striated muscle while minimizing delivery to the liver and adverse immune responses
The use of recombinant adeno-associated virus (rAAV) has emerged as a therapeutic strategy for the delivery of gene therapy, but most therapies involve systemic administration, leading to adverse immune responses. These modified rAAV present one or more amino acid substitutions in the capsid proteins, leading to surface loops alterations that result in the targeting of receptors important for cardiac and skeletal muscle viral uptake. Consequently, these particles provide improved specificity to striated muscle and higher transduction efficiencies, achieving higher efficacy, minimizing undesired delivery to the liver and reducing costs and safety risks.