Earlier this year, MIT researchers developed a way to easily and efficiently edit the genomes of living cells. Now, the researchers have discovered key factors that influence the accuracy of the system, an important step toward making it safer for potential use in humans, says Feng Zhang, leader of the research team.
With this technology, scientists can deliver or disrupt multiple genes at once, raising the possibility of treating human disease by targeting malfunctioning genes. To help with that process, Zhang’s team, led by graduate students Patrick Hsu and David Scott, has now created a computer model that can identify the best genetic sequences to target a given gene.
“Using this, you will be able to identify ways to target almost every gene. Within every gene, there are hundreds of locations that can be edited, and this will help researchers narrow down which ones are better than others,” says Zhang, the W.M. Keck Assistant Professor in Biomedical Engineering at MIT and senior author of a paper describing the new model, appearing in the July 21 online edition of Nature Biotechnology.
The genome-editing system, known as CRISPR, exploits a protein-RNA complex that bacteria use to defend themselves from infection. The complex includes short RNA sequences bound to an enzyme called Cas9, which slices DNA. These RNA sequences are designed to target specific locations in the genome; when they encounter a match, Cas9 cuts the DNA.
This approach can be used either to disrupt the function of a gene or to replace it with a new one. To replace the gene, the researchers must also add a DNA template for the new gene, which would be copied into the genome after the DNA is cut.
This technique offers a much faster and more efficient way to create transgenic mice, which are often used to study human disease. Current methods for creating such mice require adding small pieces of DNA to mouse embryonic cells. However, the process is inefficient and time-consuming.
With CRISPR, many genes are edited at once, and the entire process can be done in three weeks, says Zhang, who is a core member of the Broad Institute and MIT’s McGovern Institute for Brain Research. The system can also be used to create genetically modified cell lines for lab experiments much more efficiently.
Via Dr. Stefan Gruenwald