The way genetic illnesses are treated could be completely changed by the CRISPR molecular scissors. This is due to the fact that they can be utilized to fix particular faulty genomic regions. Unfortunately, there is a catch in some cases, such as chronic granulomatous illness, the repair may result in new genetic abnormalities. A group of clinicians and basic researchers from the University of Zurich’s (UZH) clinical research program, ImmuGene, reported this.
About one in 120,000 persons have chronic granulomatous disease, an uncommon genetic condition. Because the illness weakens the immune system, patients are more vulnerable to dangerous and perhaps fatal infections. It is brought on by the NCF1 gene’s DNA sequence lacking two letters, known as bases. The failure to create an enzyme complex that is crucial to the immune system’s fight against germs and molds is the result of this mistake.
Now, the study team has successfully inserted the missing letters in the correct location using the CRISPR method. Cell cultures of immune cells having the same genetic flaw as those in chronic granulomatous illness were used for the investigations.
This is a promising result for the use of CRISPR technology to correct the mutation underlying this disease.
Janine Reichenbach
It’s interesting to note, though, that some of the mended cells now had fresh flaws. Whole chromosomal segments where the repair has occurred were absent. The NCF1 gene’s unique genomic configuration—it appears three times on a single chromosome, once as an active gene and twice as pseudogenes—is the cause of this. These are not typically employed to construct the enzyme complex, but they share the same sequence as the faulty NCF1.
Because the CRISPR molecular scissors are unable to discriminate between the various gene versions, they can sometimes cut the DNA strand at both the active NCF1 gene and the pseudogenes. Whole gene segments could be absent or misplaced when the portions are later linked. In the worst situation, the medical repercussions can lead to leukemia development and are unexpected.
This calls for caution when using CRISPR technology in a clinical setting.
Janine Reichenbach
The scientists experimented with several different strategies, such as altered CRISPR components, to reduce the risk. Additionally, they investigated the use of protective features that lessen the possibility that the chromosome will be cut by the genetic scissors in several locations at once. Regretfully, none of these steps could totally stop the undesirable side effects.
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This study highlights both the promising and challenging aspects of CRISPR-based therapies,
However, further technological advances are needed to make the method safer and more effective in the future.
Martin Jinek
Source: University of Zurich News
Journal Reference: Raimondi, Federica, et al. “Gene Editing of NCF1 Loci Is Associated with Homologous Recombination and Chromosomal Rearrangements.” Communications Biology, vol. 7, no. 1, 2024, pp. 1-10, DOI: https://doi.org/10.1038/s42003-024-06959-z.
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