New therapeutic strategy developed for myotonic dystrophy

Published Date
Betty Kao, Royal Holloway University
Scientist observing a DNA molecule

A new version of CRISPR/Cas9 has been used to remove the toxic RNA that causes myotonic dystrophy. Although this research is still in early stages, it could lead to the development of a potential treatment.

CRISPR/Cas9 is a natural system that bacteria use to defend themselves from viral infections. It contains a section of RNA that recognises and binds to the foreign DNA of a virus. This then guides the Cas9 enzyme, which acts like molecular scissors, to cut and inactivate the viral DNA.

CRISPR/Cas9 normally targets DNA only, but Professor Yeo and his team at University of California San Diego School of Medicine have developed a new version that recognises and cuts RNA instead. They have called this RCas9, and have shown that it could be a therapeutic strategy for diseases caused by the build-up of toxic RNA, including myotonic dystrophy, Huntington’s disease and amyotrophic lateral sclerosis (ALS).

Myotonic dystrophy is caused by a build-up of RNA inside the cell nucleus. The RNA forms clumps called foci, which impair the function of an important protein called MBNL1.

MBNL1 naturally binds RNA and regulates how it is processed. In myotonic dystrophy, MBNL1 binds to the RNA foci instead of its normal RNA binding sites, resulting in RNA that is not processed properly. This is thought to cause to the body-wide symptoms of myotonic dystrophy.

In this new study, Professor Yeo and his team tested the RCas9 system in cells originating from people with myotonic dystrophy type 1 and type 2. They found that it eliminated over 95% of the RNA foci inside the cells. This restored the function of MBNL1, resulting in normal processing of RNA.

While this study is an important proof-of-principle that the RCas9 system works, more research is needed before it can be tested in human trials. Professor Yeo has set up a company called Locana that will carry out the preclinical research required to advance this new technology from the laboratory to the clinic.

The study was published in the scientific journal, Cell.

Further information

Read this press release from University of California San Diego School of Medicine

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