Researchers at ETH Zurich have made a significant breakthrough in genetic research by developing a technique that allows for the simultaneous modification of multiple genes in the cells of adult animals. This innovative approach, using the CRISPR-Cas gene editing tool, creates a mosaic-like pattern that simplifies the study of genetic diseases. By modifying multiple genes in a single animal, researchers can gain new insights into the complexity of genetic disorders while reducing the number of experiments with animals required.

Traditionally, scientists have studied the genetic origins of diseases by focusing on a single gene. However, many diseases are influenced by multiple genes, making it difficult to determine the contribution of each gene to the condition. This would normally require numerous experiments with animals, each focused on a specific genetic modification.

Led by Professor Randall Platt, the researchers developed a method that uses CRISPR-Cas to make changes to multiple genes in the cells of a single animal, creating a mosaic-like pattern. While each cell has only one altered gene, different cells within an organ have distinct modifications, allowing for precise analysis of individual cells. This breakthrough enables researchers to study the effects of various genetic changes in a single experiment, significantly simplifying the research process.

For the first time, the ETH Zurich team successfully applied this technique in adult mice. They used adeno-associated viruses (AAV) as a delivery system to instruct the cells on which genes to modify. By infecting the mice with a mixture of viruses carrying different instructions, the researchers were able to deactivate different genes in the brain cells. This method proved effective in providing new insights into the 22q11.2 deletion syndrome, a rare genetic disorder in humans. The researchers discovered that three genes within a specific chromosomal region play a significant role in the malfunctioning of brain cells and their association with conditions such as schizophrenia and autism spectrum disorders.

The potential applications of this technique are vast, as it can be used to study other genetic disorders involving multiple genes. By gaining a deeper understanding of abnormal gene activity in various diseases, researchers can develop targeted medications to counteract these abnormalities. Furthermore, this method allows scientists to directly study fully-developed animals, reducing the need for experiments on embryos or cultured cells.

As researchers continue to refine this technique, the number of modified genes could increase from the current 29 to several hundred. This advancement represents a substantial leap forward in genetic research, offering new possibilities for studying the complexity of genetic diseases and developing specific treatments.

– ETH Zurich Research News
– Nature Journal