First gene editing drug based on CRISPR/Cas receives recommendation for approval: Safety in focus

New scientific publication with EB House contribution

CRISPR/Cas is currently the most promising method for precisely modifying information in our genetic material, DNA. This technology targets and corrects gene mutations responsible for diseases using enzymes, the gene editing tools likened to molecular scissors. Researchers at the EB House are focusing on using this method to treat different forms of Epidermolysis Bullosa (EB) by editing the DNA of the patient's skin cells.

However, despite their precision, CRISPR/Cas enzymes may occasionally induce unintended alterations in the cell's chromosomes, the carriers of genetic information. These unintended alterations, known as off-target effects, can occur in areas of the DNA that were not meant to be altered. Additionally, there is a risk of on-target effects when the Cas enzyme binds inaccurately to the DNA, causing unintended changes in the targeted area.

To better understand and address these potential side effects, scientists from Freiburg, Germany, have developed an analysis method called Dual CAST. This method allows for precise detection of both intended and unintended alterations in the DNA. It is proven to be more sensitive in detecting DNA changes compared to traditional sequencing techniques. In collaboration with the EB House Austria, Dual CAST was tested for the first time in a laboratory study. EB skin cells harbouring known mutations were treated with various CRISPR/Cas enzymes to achieve specific changes in the DNA. Researchers then used Dual CAST to examine the genome for both desired and potential unwanted changes.

All gene editing strategies led to the desired DNA modifications. Interestingly, only one specific CRISPR approach that uses two specific cutting enzymes (double nickases) did not cause any unwanted changes in the chromosomes. This suggests that the double nickase approach could be highly efficient in correcting mutations without causing harmful off-target effects, and might be safer than traditional CRISPR/Cas editing. However, they did observe some on-target DNA changes, such as large deletions, which are known risks associated with gene editing.

While gene therapy procedures using CRISPR/Cas are becoming more effective and safer, further research is needed to fully understand and minimize the risks associated with these technologies. Dual CAST shows promise as a tool to support the development of safer gene editing therapies.

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