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Treating Common Heart Disease with CRISPR-Cas9 Gene Editing
Researchers from UT Southwestern successfully corrected mutations responsible for a common inherited heart condition called dilated cardiomyopathy (DCM) in both human cells and mouse models. Their findings, published in Science Translational Medicine, provide promising results for the implication of gene therapy in DCM and may become a highly feasible treatment option in the future.
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The Causes and Prevalence of DCM
Dilated cardiomyopathy is characterized by dilation and impaired contraction of one or both ventricles. Affected patients have impaired systolic function and are highly susceptible to sudden cardiac death.
As one of the most common cardiac diseases, DCM has a high prevalence rate of one per 250 people. Cardiac transplantation at a young age is the only currently effective treatment for this disease. However, a shortage of donor organs is always the main obstacle.
DCM is caused by mutations in a gene known as RNA binding motif protein 20 (RBM20), which affects the production of hundreds of proteins in cardiac muscle cells responsible for the heart’s pumping action. With their previous experience in halting the progression of Duchenne muscular dystrophy in animal models using CRISPR, the team sees the potential of this gene-editing tool to correct mutated genes in DCM.
A Promising Tool for Familial Diseases
To determine the feasibility of this approach, the team used a virus to deliver CRISPR-Cas9 components to cardiac muscle cells derived from human cells carrying two different types of DCM-causing mutations. CRISPR is used to swap a single nucleotide to correct one type of mutation.
In another set of cells, researchers replaced a piece of DNA from mutated RBM20 with a healthy segment of this gene. After CRISPR-Cas9 treatment, the mutant cells gradually lost characteristics inherent to DCM, meaning the protein produced by RBM20 moved to its normal place in the nucleus, and the cells could make healthy proteins.
As part of an in vivo experiment, the 1-week-old mice carrying one of these mutations did not develop enlarged hearts and had normal life spans after receiving CRISPR-Cas9 treatment. On the contrary, untreated mice had symptoms mirroring those of human DCM patients.
To sum up, these findings demonstrated the potential of precise correction of genetic mutations as a promising therapeutic approach for DCM. However, there is still a long way to go before it becomes a standard treatment, as the sustainability of CRISPR-Cas9 and the minimal dose needed have yet to be determined. Nevertheless, scientists see the great potential of gene editing to treat a variety of other familial diseases.
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