When Renzhi Han, PhD, was welcomed to Indiana University School of Medicine he declared the long-term research goal within his lab would be to shed light on the underlying causes of muscular dystrophy and develop innovative gene therapies to support the children and families facing these devastating genetic muscle diseases.
Now, in 2026, Han and his lab are doing just that with the help of a new four-year $2.6 million grant from the National Institutes of Health (NIH).
“My commitment stems from the stark gap between genetic potential and clinical reality,” said Han, professor of pediatrics at IU School of Medicine and a principal investigator in the Herman B Wells Center for Pediatric Research Gene and Cell Therapy Research Program. “Seeing how the absence of dystrophin devastates young lives made finding a cure an urgent personal mission.”
Duchenne muscular dystrophy (DMD) is a fatal muscle degenerative disease caused by mutations to the DMD gene. This results in the dysfunction or absence of the dystrophin protein, which protects muscle fibers from tearing when they contract and relax.
Muscle weakness symptoms typically begin in male children between 2 – 3 years of age. For those with the disease, the absence of dystrophin proteins eventually leads to respiratory and heart failure.
In June of 2023, a revolutionary gene therapy was approved that delivered micro-dystrophin via adeno-associated virus (AAV) into DMD patients. The process involves using a safe delivery virus (the AAV) to carry micro-dystrophin proteins into the body. Although this therapy initially served as a great first step in the DMD gene therapy, the results were less than satisfactory. Because micro-dystrophin lacks many important functional segments of the full-length dystrophin, it leaves the organs only partially protected and full-length dystrophin cannot fit within the delivery virus due to the AAV’s microscopic size. Another problem with the delivery model is that the large doses of AAV required for the therapy often elicit dangerous immune responses within the patient and even organ toxicity.
“Witnessing the high-dose toxicities and partial protection offered by early micro-dystrophin trials convinced me that we shouldn't settle for partial fixes,” Han said. “I was inspired to pursue what many considered impossible: delivering the complete, fully functional protein safely.”
Thanks to advances in delivery systems such as protein trans-splicing technology and myotropic AAV capsid engineering, which would allow for complete dystrophin proteins to be delivered into the body, and the new grant funding from the NIH, Han’s lab is now able to explore the feasibility of delivering full-length dystrophin in animal models of DMD.
“This grant is a pivotal bridge between lab proof-of-concept and future clinical translation,” Han stated. “This funding allows us to test a new ‘delivery truck’ system that splits the full-length, completely functional protein into three pieces, delivers them using more efficient vehicles and reassembles them scarlessly inside muscle and heart cells. Ultimately, it gives us the resources to make this complete treatment safer and more effective for future clinical trials.”
When it comes to the future of DMD therapies, Han sees the horizon shifting from partial compromise to complete biological restoration.
“We are moving past the era where we have to choose between a truncated protein or no treatment at all,” he said.
With the next-generation of capsid engineering and split-vector technology, Han said it is possible to deliver the full-length dystrophin protein directly to skeletal muscles, the diaphragm and the heart at safer, lower viral doses. Han and his team are working with relentless urgency to turn these advances into safe, transformative treatments for DMD patients.
