Purposefully changing a gene’s DNA sequence or gene editing is a good tool for understanding for therapeutic purposes making changes in an individual’s DNA and how mutations cause disease. A team led by Guoping Feng, James W. (1963), and Patricia T. Poitras, Professor in Brain and Cognitive Sciences at MIT, has developed a novel method of gene editing that can be used for both purposes.
“This technical advance can accelerate the production of disease models in animals and, critically, opens up a brand-new methodology for correcting disease-causing mutations,” says Feng. On May 26, 2021, the new findings were published online in the journal Cell.
A significant purpose of the Feng lab is to precisely define what goes wrong in neuropsychiatric disorders and neurodevelopmental by engineering animal models that carry the gene mutations that cause these disorders in humans. New models can be created with gene-editing tools by injecting embryos and a piece of DNA carrying the desired transformation.
The gene-editing tool CRISPR in one such method is programmed to cut a targeted gene, and natural DNA mechanisms are activated by this, which repair the broken gene with the injected template DNA. From the engineered cells, offspring is generated capable of passing the genetic change on to further generations. It creates a stable genetic line in which therapies and diseases are tested.
CRISPR has increased the process of generating such disease models, but still, the process can take months or years. The reason for inefficiency is that the desired DNA sequence change is not undergone by many treated cells, and the change only occurs on one of the two gene copies.
To increase the efficiency of the gene-editing process, initially, it was hypothesized by the Feng lab team that adding RAD51 (a DNA repair protein) to a standard mixture of gene editing tools CRISPR would increase the chances that a cell would undergo the desired genetic change.
As a test case, the rate at which they could insert a mutation in the gene Chd2 associated with autism was measured by them. What remained unchanged was the overall proportion of embryos that were correctly edited. To their surprise, the desired gene edit on both chromosomes was carried by a higher percentage. Test with different genes gave the same result.