Genre repair in a clinical environment harbors risks

The CRISPR gene scissors can be used to correct mutations in DNA very precisely and thus eliminate the causes of hereditary diseases. However, a team of basic researchers and doctors from the ImmuGene Clinical Research Priority Program at the University of Zurich(UZH) has now discovered in laboratory experiments that this can lead to unintended and serious new genetic defects.

According to a UZH report, the discovery was made while correcting the DNA sequence of a gene called NCF1. This sequence is responsible for the rare hereditary disease chronic granulomatosis. Team leader Janine Reichenbach describes the successful repair as a "promising result". She is Professor of Somatic Gene Therapy at the University Children's Hospital Zurich and the Institute of Regenerative Medicine at UZH.

However, the repaired cells then showed defects. The reason for this is a special feature of the NCF1 gene: it is present three times on the chromosome, once as an active gene and twice in the form of so-called pseudogenes.

Because the CRISPR gene scissors cannot distinguish between them, they occasionally cut the DNA strand in several places. When they are reassembled, entire gene segments are arranged incorrectly or are missing. This can have unforeseeable medical consequences. Various attempted measures have not yet been able to eliminate this risk.

"This study shows both the promising and the challenging aspects of CRISPR-based therapies," summarizes co-author Martin Jinek, Professor at the Institute of Biochemistry at UZH. "But more technological advances are needed to make the method safer and more effective in the future." ce/mm