Dr. Duan received his medical training in China from the West China University of Medical Sciences in 1987 and his Ph.D. from the University of Pennsylvania in 1997. His major research interest is to develop adeno-associated virus (AAV)-based gene replacement and gene repair therapy for Duchenne muscular dystrophy. Dr. Duan has pioneered dual AAV-mediated mini-dystrophin gene therapy. The micro-dystrophin technology developed in the Duan lab is now in a phase I clinical trial. In regards to gene editing, the Duan lab has recently demonstrated AAV-mediated dystrophin editing in muscle stem cells in vivo. The latest work from the Duan lab showed that a one-time intravenous injection of the AAV CRISPR therapy can improve muscle and heart function in the DMD mouse model for 18 months. Dr. Duan has received many awards including Spurgeon Distinguished Medical Research Award in 2004, Outstanding New Investigator Award from the American Society of Gene Therapy in 2006, Chancellor’s Award for Outstanding Research and Creative Activity from the University of Missouri in 2009, Honorary Medical Alumni Award, University of Missouri in 2017, and Excellence in Research Mentoring of Trainees Award, University of Missouri. Dr. Duan has published more than 150 peer-reviewed papers and edited two books.
CRISPR Editing Therapy for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common lethal muscle disease affecting ~250,000 to 300,000 boys and young men worldwide. DMD is caused by frame-shifting mutations in the dystrophin gene. CRISPR-mediated genome editing holds promise to restore the reading-frame of the mutated dystrophin gene. To explore this innovative therapeutic modality, we generated adeno-associated virus (AAV) vectors that express the Cas9 endonuclease and the guide RNA (gRNA). The gRNA was used to direct Cas9 to the selected targets in the dystrophin gene to directly remove the mutation or to modulate genomic splicing signals to allow production of an in-frame dystrophin transcript. DMD is a chronic disease affecting all muscles in the body. An effective therapy for DMD requires life-long treatment. Targeting satellite cells, the muscle stem cells, will allow regenerated myofibers to express dystrophin. We examined whether satellite cells can be edited by free muscle grafting. Our results suggest that AAV can transduce and edit satellite cells. To study long-term benefits, we treated 6-week-old mdx mice, a DMD model. At 18 months after therapy, we observed bodywide dystrophin restoration. Importantly, CRISPR therapy improved muscle force and heart function (Funded by NIH AR69085 and DOD MD150133).
Disclosure: D.D. is a member of the scientific advisory board for Solid Biosciences.