(ORDO NEWS) — Researchers at ETH Zurich have developed a groundbreaking method using CRISPR-Cas gene scissors to make multiple gene changes in the cells of a single animal. This new technique, the first to be successfully used in adult mice, will greatly simplify and speed up research using laboratory animals.
The challenge of studying multiple genes
Understanding the genetic origins of diseases can be challenging because many diseases are determined by multiple genes. This complicates the task of scientists trying to determine the contribution of any one gene to the development of a particular disease.
Traditionally, researchers have to conduct many experiments on animals, each aimed at modifying different genes.
A revolutionary approach
Led by Randall Platt, professor of biological engineering at ETH Zurich, the team used CRISPR-Cas gene scissors to simultaneously make dozens of gene changes in the cells of a single animal. Although only one gene is changed in each cell, different cells within an organ change in different ways.
This allows precise analysis of individual cells and the study of the effects of changing multiple genes in a single experiment.
Successful use in adult mice
In a recent report published in the journal Nature, ETH Zurich researchers reported the success of using this approach in living animals, specifically adult mice. In previous studies, similar results were obtained only on cells in culture or animal embryos.
Use of adeno-associated virus (AAV) delivery strategy
To modify mouse cells, researchers used adeno-associated virus (AAV) as a delivery strategy. AAV can be targeted to any organ and has been prepared in such a way that each viral particle carries information about the destruction of a specific gene.
The mice were infected with a mixture of viruses carrying different gene-killing instructions, allowing the researchers to turn off different genes in the cells of the same organ. In this study, the scientists focused on the brain.
Discovering new clues to a rare genetic disease
Through a study in mice, scientists from ETH Zurich, together with colleagues from the University of Geneva, have obtained new information about a rare genetic disease known as 22q11.2 deletion syndrome. This syndrome is characterized by a variety of symptoms that are often misdiagnosed as other diseases such as schizophrenia and autism spectrum disorders.
Although it was previously known that a chromosomal region containing 106 genes was responsible for this disease, the specific role of each of them was unknown.
Identifying key genes and dysfunction in brain cells
In their study, the scientists focused on 29 genes in this chromosomal region that are active in the mouse brain. They modified one of these 29 genes in each individual mouse brain cell and then analyzed the RNA profiles of those cells. The analysis identified three genes that are largely responsible for the brain cell dysfunction associated with this disorder.
The researchers also found patterns in the mice’s cells that were reminiscent of schizophrenia and autism spectrum disorders. If one of the three genes was already known, then the other two had not previously attracted much attention from scientists.
This groundbreaking research opens up new possibilities for understanding and studying complex diseases with multiple genetic factors. It allows scientists to make significant progress in identifying the specific role of each gene in various diseases, which will ultimately lead to improved diagnosis and treatments.
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