Researchers have adapted CRISPR-Cas9 technology to target somatic mutations that generate motifs adjacent to protospacers (PAMs) in pancreatic cancer genomes. The researchers developed a bioinformatics pipeline called PAMfinder to identify these mutations in the cancer genome. By designing sgRNAs to target these novel PAMs, CRISPR-Cas9 can selectively introduce DSBs into cancer cells, destroying them while sparing normal cells. This method exploits the high mutational load of cancer cells, particularly in non-coding regions, to create a wide range of specific targets for CRISPR-mediated cell killing. Functional assays in three pancreatic cancer cell lines demonstrated 69-99% selective cell death using 4-9 sgRNAs designed to target PAM sequences. In addition, the absence of off-target effects confirmed the strategy's efficacy, demonstrating high specificity and a substantial reduction in cancer cell viability.
Dinah Farrington
2mo
This is terrific!
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2moThis is fascinating! The precision and specificity of this approach using CRISPR-Cas9 to target somatic mutations in pancreatic cancer is truly groundbreaking. The development of PAMfinder to identify these mutations and the subsequent design of sgRNAs to selectively induce DSBs in cancer cells is a brilliant strategy. The high success rate in functional assays and the absence of off-target effects are particularly impressive. Could this method potentially be adapted for other types of cancer with high mutational loads?