Decoding Disease: UC San Diego’s Leap in Gene Editing

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UC San Diego researchers developed new genome editing tools, multiplexed orthogonal base editors , which efficiently install multiple point mutations at once. This tool enhances the understanding and modeling of genetic diseases by allowing for controlled variant installation in the lab, offering a new approach to studying complex diseases. Credit: SciTechDaily

Traditional methods for modeling or correcting mutations in live cells are notably inefficient, particularly when installing multiple point mutations simultaneously across the genome. However, researchers from the University of California San Diego have developed new genome editing tools called multiplexed orthogonal base editors that can efficiently install multiple point mutations at once.

Although relatively straightforward, double-stranded breaks can be toxic to cells. This kind of gene-editing can also lead to indels — randometions — where the cell is not able to perfectly repair itself. Editing multiple genes in CRISPR-Cas9 multiplies the risks. The differences are stark: when CBE and ABE are given together not using MOBE, crosstalk occurs up to 30% of the time. With MOBE, crosstalk is less than 5%, while achieving 30% conversion efficiency of the desired base changes.

 

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