A new gene delivery vector can make gene therapy of muscle diseases safer and more effective

Inherited muscle diseases can cause progressive muscle atrophy, often leading to early death, with few treatment options and no cure

Researchers from MIT and Harvard University and Harvard University have developed a new family of Adeno-Associated Viruses (AAVs) to improve the target of muscle tissue, safer and more effective

In a study published in the journal Cell, Sharif Tabebordbar, a research scientist at Harvard University's Broad College, and collaborators described how they modified the outer protein shell of AAV, namely Capsid to create MyoAAV

Using MyoAAV, researchers specialize therapeutic genes or the CRISPR-Cas9 gene editing system for muscle cells

These findings are the result of 10 years of work by Tabebordbar

"I watched my dad getting worse day by day

"There is a lot of capsid engineering research, we have learned a lot from it, but what we have done here is very comprehensive

Target muscle

The field of gene therapy has made significant progress in restoring functional copies of dysfunctional genes in a series of genetic diseases

"For the past 15 years, scientists have been conducting preclinical work on in vivo gene therapy and have made tremendous progress

Tabebordbar and his team started with AAV9, a gene delivery vector commonly used in gene therapy, and used DELIVER to improve its ability to deliver genes to muscle cells

The researchers first generated millions of different AAV capsids by adding random amino acid strings to the AAV capsids exposed on the surface of the virus and bound to the cells

"Our method is unique because we screened a large number of capsids and used very strict selection criteria

Mouse gene repair

In a mouse model of Duchenne muscular dystrophy, MyoAAV with CRISPR-Cas9 resulted in a more extensive repair of the dysfunctional gene dystrophin in muscle tissue compared to traditional AAV9 with CRISPR-Cas9

In collaboration with the laboratory of Alan Beggs at Boston Children’s Hospital, the research team found that MyoAAV was also effective in treating X-linked myotube myopathy (XLMTM) in mice, which was found to be effective in these animals after about 10 weeks.

MyoAAV, designed for non-human primates, can also deliver genes into the muscles of these animals, and its efficiency is much higher than the natural capsids used in current clinical trials

"All these results demonstrate the broad applicability of MyoAAV vectors to muscles
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These vectors play a role in different disease models and different ages, strains, and species, which proves the robustness of the AAV family," the joint senior of the study The author, Professor and Co-Chair of Harvard University's Department of Stem Cell and Regenerative Biology, said Amy Wagers
.
"We have a lot of information about this type of carrier, and many exciting new studies can be carried out in this field
.
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Article retrieval:

Journal

Cell

DOI

10.
1016/j.
cell.
2021.
08.
028