Gene therapy is a recent development in the industry, and it is one that has brought hope to many people who live with a genetic condition without a viable treatment option. Rare disease patients are especially excited, as this new technology could provide therapies for the 95% of conditions that do not currently have any treatments. According to Medical Xpress, a new approach to gene therapy that utilizes CRISPR/Cas9 technology could enable therapies for a number of rare diseases.
New Approach to Gene Therapy
A team of researchers from Penn State discovered this new approach through a proof-of-concept study that was published in Molecular Therapy. Using both human tissue and mouse models, the researchers were able to replace malfunctioning genes with the working versions. This means that rare diseases caused by a single-gene mutation, such as cystic fibrosis or sickle cell anemia, may have new treatment options soon.
This new strategy takes on two of the issues that exist with current gene editing: homology-directed repair cannot target most adult tissue and is difficult to use in single genes that can mutate in various ways. Homology-directed repair is the standard in gene editing as of now, and while it has led to many great developments, it still has its drawbacks.
Called CRBR, the new approach designed by the Penn State researchers takes a condensed form of the normal, functioning gene and places it between the altered gene’s promoter region using non-homologous end joining, a cellular repair pathway. At the end of the condensed gene is a terminat0r sequence, which effectively stops the remaining mutated gene from expressing itself. This makes it much easier to use in genes that can mutate in multiple ways, and it can also be used in adult tissue.
Testing the Approach
Multiple proof-of-concept experiments were performed to ensure that this approach was actually viable. First, they utilized a mouse model of Wolcott-Rallison syndrome, a recessive condition characterized by skeletal issues and neonatal diabetes, which is the result of a mutated PERK gene. After using the CRBR approach to insert a functional version of the PERK gene into healthy mice, the researchers bred them with mice affected by Wolcott-Rallison syndrome. The resulting offspring did not present the symptoms of the condition, indicating that the gene-editing worked.
The researchers used human tissue next, specifically the gene responsible for insulin. Through the use of a green fluorescent protein marker gene sequence, the researchers were able to see that the inserted DNA sequence only expressed between the coding sequence and gene promoter in the insulin gene. This is more positive news, as it means that their CRBR approach is strictly regulated.
Looking Forward
The team of researchers working on this product is very happy with this work, as their new approach to gene editing stands to improve on the current standard of care. Not only does it solve two common errors, but it is much more tolerant of any mutations that are the result of an issue in treatment.
More research must be done into this form of genetic editing, but the current work looks very promising. This form of gene therapy may be able to create treatments for various rare diseases.
