Scientists have taken another giant leap towards using the gene-editing system, CRISPR. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. In genome engineering fields it refers to various systems that allow scientists to edit DNA at precise locations.
The systems can also be used as a diagnostic tool. CRISPR made headlines when it was first published in about 2002 and was hailed as the answer to curing all diseases.
However, as research has progressed, CRISPR and its uses are much more complicated than simply deleting the genes that cause disease. One of this hurdle is the fact that editing cut-up genes takes a really long time.
Scientists at UCLA have now come up with a way to edit multiple genes at once. Currently, the tracking of the impact of changes made to genes using CRISPR is done individually.
New system radically speeds up impact tracking
Each edit is analyzed one at a time, a process that can take weeks. The latest development by the scientist now means that they can monitor the outcome of tens of thousands of gene edits at the same time as it currently takes to analyze just a few.
“For several years, scientists have used CRISPR to cut many genes at one time,” said lead author Leonid Kruglyak, chair of human genetics at the David Geffen School of Medicine at UCLA.
“But there was a lack of CRISPR methods to edit many genes at once. Our lab is the first to develop a large-scale technique for achieving this in cells structured like human cells.” The breakthrough will allow scientist to better identify the genetic changes most likely to harm cells and contribute to disease.
“For CRISPR to introduce edits to the genome properly, each cell needs to receive the right combination of guide and patch,” said first author Meru Sadhu, a postdoctoral researcher in Kruglyak lab. He further added, “Delivering the pairs correctly to thousands of cells at the same time posed a complicated scientific puzzle.”
The new method developed by UCLA allows for the physical connection of thousands of guides to their partner patches, ensuring a perfectly matched set is delivered to each cell. To test the new method, the team studied a class of genetic mutations suspected to be harmful to cells.
Good and bad cells now quickly identified
The experiment was performed on yeast because cellular changes in response to gene alterations happen quickly in yeast and are easy to observe. Millions of yeast cells were grown inside a flask of fluid, the researchers then used CRISPR to deliver a customized set of paired guides and patches to each cell.
About 10,000 distinct mutations were explored simultaneously. CRISPR was instructed by the guide and patch on where to snip the gene and the edit to introduce. After four days, the team was able to identify which cells died or survived.
“We were surprised to find that some genes believed to be essential for cell function actually aren’t,” Sadhu said. “In other genes, only a part of the protein is essential, while the rest can be chopped off and the cell will still survive.”
The technique should allow scientists to quickly identify the most damaging genetic edits from the harmless. “We can now edit the genome in thousands of different ways, while observing positive or negative effects on cells,” said Kruglyak, who is also a Howard Hughes Medical Institute investigator.
“Our ultimate goal is to help scientists zero in on the genetic culprit for a disease, leading doctors to a firm diagnosis and allowing patients to obtain the most effective treatment.” The full report can be read in Nature Genetics.