John Leonard, PhD, on an AAV Approach to Exon 51 Skipping in DMD


The chief scientific officer of LocanaBio discussed preclinical data with an AAV-delivered, snRN, exon 51 skipping approach presented at ASGCT 2023.

“The ASO approach makes a lot of sense. Second generation ASOs using targeted delivery, we'll just have to wait and see how they pan out clinically. But, at the end of the day, we know that AAV vectors can get effectively to muscle, so we have a strong reason to believe that this will translate from the mouse studies.”

Exon 51 skipping is a validated approach taken by the approved antisense nucleotide (ASO) drug eteplirsen (EXONDYS 51; Sarepta Therapeutics) for treating Duchenne muscular dystrophy (DMD). LocanaBio is investigating exon 51 skipping by use of adeno-associated virus (AAV9) gene therapy carrying multiple small nuclear RNAs (snRNAs), which may yield a greater percentage of exon skipping compared to the ASO approach.

The company presented preclinical data from mouse models validating the AAV9 approach at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California. CGTLive spoke with LocanaBio’s chief scientific officer, John Leonard, PhD, to learn more about the new approach and its potential advantages over the ASO approach. He also touched on advantages on the exon skipping approach as compared to microdystrophin gene therapy approaches in the DMD population with the appropriate mutation, including not inducing supraphysiological levels of microdystrophin and potential complciations that may ensue from that. He also touched on efforts to diagnose DMD early in the disease course as all genetic approaches are more effective when delivered earlier.

Click here to read more coverage of the ASGCT 2023 meeting.

Markmiller RL, Nachtrab G, Geddes C, et al. Small nuclear RNA-mediated exon 51 skipping AAV9 gene therapy for the treatment of Duchenne muscular dystrophy. Presented at: ASGCT 2023 Annual Meeting; May 16-20; Los Angeles, California. Abstract #1198.
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