From The Editor | June 24, 2024

mRNA Delivering Full-length Dystrophin for DMD


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1


Cell & Gene: The Podcast features some of the CGT sector’s brightest leaders who share their expertise on the timeliest topics and trends. If you can’t tune in to every episode, I’ve got you covered. Here are highlights, quotes, and more from a recently aired episode.

The Episode:

Developing an mRNA Therapy for DMD with Elixirgen Therapeutics' Aki Ko

Guest At-A-Glance

Aki Ko has served as Chief Executive Officer and Chair of the Board of Directors since May 2017, when he co-founded the company. Previously, Mr. Ko served as Chief Operating Officer for Elixirgen, LLC, the parent company of Elixirgen Therapeutics, and President of Elixirgen Scientific, LLC, a provider of stem cell reagent kits and related services. In his previous roles, Mr. Ko was responsible for operations and business development at Elixirgen, LLC and Elixirgen Scientific. Mr. Ko earned a Bachelor of Science degree from the University of Virginia, where he cultivated his interest in biology.

Organization At-A-Glance

Elixirgen Therapeutics is a clinical-stage RNA therapeutics company focused on the discovery and development of cell and gene therapies. The Company is advancing three technologies to develop therapeutics for a broad spectrum of diseases including rare and genetic diseases, and aging-related disorders.

Episode Highlights

Meeting the Needs of the Duchenne muscular dystrophy (DMD) Patient

You’ll find that the common theme throughout this episode is the emphasis on the patient. Ko stresses that while there is so much active development for patients with DMD, there is still a highly unmet need, particularly for the non-ambulatory patient and for the older population. This is because most of the existing therapies target ambulatory and younger pediatric patients.

Breaking Down the Poster Presentation

Ko explained that the current set of approved drugs for DMD includes four exon-skipping drugs and one AAV-microdystrophin drug that supplements a missing dystrophin protein with its shortened version. It is conceivable that delivery of a normal, full-length dystrophin protein would address issues seen with these other dystrophin replacement approaches. Back in March at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, Elixirgen shared its poster presentation on its proprietary Bobcat mRNA technology. Bobcat mRNA is designed to deliver large protein payloads (over 13 kb), and results show that a Bobcat mRNA encoding a full-length dystrophin protein can restore muscular function in a mouse model for DMD. Ko notes that Elixirgen’s full-length dystrophin approach may be complementary to others currently approved or in development or may even mitigate some of their issues.

Top Quotes

10:22: At the conference, we showed a preclinical proof of concept for this full-length dystrophin expression using Bobcat mRNA. And so this was first expression in vitro, but also expression in vivo. And, both of these are important data points for development for a therapeutic for DMD. And so, particularly for in vivo, mouse skeletal muscle was injected with bobcat mRNA expressing DMD.  And we were able to see proper localization of the full-length dystrophin in vivo. We also shared functional data. And we used D2.mdx mice, which are a DMD disease model mouse that show a more severe phenotype than the standard .mdx model that is used for much of the research.

There’s More Where That Came From

This is just some of what Ko shares during our chat. We also discuss the challenges with delivery. Tune in to the full-length episode to hear him explain the advantage of the mRNA approach over the AAV approach.