Get Your Cell K.O. in the First Round
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Recent advances in the development of genome-editing technologies based on programmable nucleases have substantially improved our ability to make precise modifications in the genomes of eukaryotic cells. Specifically, programmable nucleases enable precise genome editing by creating DNA double-strand breaks at specific genomic loci.1 In the absence of a repair template, the DNA lesion will be repaired through nonhomologous end joining, a mechanism that religates the 2 free double-strand break ends. Nonhomologous end joining is, however, error prone, often creating small insertion or deletion mutations bridging the break site.2 If these insertion or deletion mutations are introduced in the coding sequence of a gene, they can potentially lead to loss-of-function mutations into the targeted gene, thus leading to its permanent inactivation. This approach can then be applied to different cell types where it will be extremely efficient to knockout a gene of interest.
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Genome-editing technologies are, thus, broadening our ability to elucidate the contribution of genetics to disease, including cardiovascular, by allowing the unprecedented and fast creation of appropriate cellular or animal models of pathological processes.3,4 Their application is particularly appealing into pluripotent stem cells (such as human induced pluripotent stem cells [hiPSCs]) to perform functional investigations on a putative gene (or a mutation) in a genetically modified cellular model of cardiac or vascular disorders. However, with ≈25 000 annotated genes in the human genome and >3700 already linked to disease phenotypes, the …