CRISPR for DuchenneGenome editing technology to correct the mutated dystrophin gene
The Duchenne Research Fund has awarded a £200,000 grant to the team at the Hospital for Sick Children in Toronto, Canada (‘Sick Kids’), who are working on using CRISPR/Cas9 technology to correct duplication mutations for Duchenne.
Sick Kids’ incoming President and CEO Dr Ronald Cohn has already had significant success as the first researcher to correct duplications in human cells in the lab, using CRISPR technology. Dr Cohn, Daria Wojtal and their team have since been working to achieve the same results in mice that have Duchenne duplications, and have so far seen exciting results.
The aim is to translate this into boys and young men with Duchenne in the future.
Duchenne muscular dystrophy is caused by a mutation in the dystrophin gene, which results in the absence of full-length dystrophin protein, needed to protect muscles. Without this protein, the muscles waste.
Current gene therapy clinical trials involve administering a ‘microdystrophin’ – a shortened form of the correct gene – with the aim of overriding the effect of the mutated gene. The dystrophin gene is the longest known gene in the body, and a full-length version is too large to deliver into the cells using existing drug delivery technology, so this shortened form is used.
However, recent advances in genome editing technologies based on CRISPR/Cas9 technology have the potential to correct the gene, returning it to the correct full-length version of the gene. Rather than ‘sending in’ a shortened version of the gene, this more recent approach aims to correct just the mutated part of the gene. In the case of patients whose mutation is a duplication (where a part of the genetic code is repeated twice) the CRISPR approach entails sending in ‘genetic scissors’ into the cells to ‘cut out’ the duplicated part of the gene, restoring the correct full-length dystrophin.
Check back here and in our news section in the coming months to find out how this project is progressing.
Funded in 2018-19
How does CRISPR differ from other treatment approaches?
The image below provides a visual representation of how CRISPR differs from treatments currently in use or being trialled for Duchenne.
Within our genes, DNA code (represented in the image by a cookbook), is transcribed into mRNA (akin to the reciting of a recipe). This then provides the information needed for the correct protein to be produced (the cake). When a mutation is present, this process is disrupted, and the protein is not produced adequately or at all. In the case of Exon Skipping, Stop Codon Readthrough and gene therapy treatment approaches for Duchenne, the result is a partial cake. As explained previously, in the case of gene therapy, this is due to the use of a shortened form of dystrophin. The CRISPR approach aims to produce the whole cake, thereby maximising the amount of protein produced.
News from the Hospital for Sick Kids, Toronto
Solid Biosciences announces preliminary gene therapy clinical trial results and intention to dose escalate
Solid Biosciences has announced preliminary data from its gene therapy clinical trial, IGNITE DMD …
Five years ago we identified gene therapy as a viable treatment for Duchenne. Today we are reflecting on the exciting and inspiring events of the past week in the gene therapy arena which are now bringing hope and cautious optimism to the Duchenne community. We have...
Message from Solid Biosciences: "We’re pleased to share with you that the FDA has lifted the clinical hold on IGNITE DMD, our clinical trial investigating SGT-001 as a potential treatment for Duchenne muscular dystrophy (DMD). SGT-001 is a microdystrophin gene...
Solid Biosciences recently reported that it has raised up to $50 million which will enable the biotech to continue to advance its programs for Duchenne muscular dystrophy, including development of a microdystrophin gene. We are forever grateful to our incredible...
We are thrilled that the money raised through the Duchenne Research Fund’s 2013 dinner and donations since then have enabled us to seed fund the incredible Solid GT project, which has today received industry investment (read the press release below). While gene therapy is an exciting piece of the puzzle for beating Duchenne for all boys, it is now more critical than ever that we continue to raise vital funds to push Duchenne therapies into clinical trial as quickly and safely as possible and to get them to our boys NOW.
The Duchenne Research Fund is incredibly proud of Dr Dongsheng Duan – an important Scientific Advisory Board member of Solid GT, a gene therapy programme pioneered by Solid Biosciences and that we helped to fund. Dr Duan’s latest gene therapy work on muscular dystrophy dogs is set to significantly impact 100% of the Duchenne population.
He also recently received a five-year, $3 million grant from the NIH (National Institutes of Health) …
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