Unlabelled: Although genomes encode instructions for mammalian cell differentiation with rich syntactic relationships, existing methods for genetically programming cells have modest capabilities for stepwise regulation of genes. Here, we developed a sequential genetic system that enables transcriptional activation of endogenous genes in a preprogrammed, stepwise manner. The system relies on the removal of an RNA polymerase III termination signal to induce both the transcriptional activation and the DNA endonuclease activities of a Cas9-VPR protein to effect stepwise progression through cascades of gene activation events. The efficiency of the cascading system enables a new dimension for cellular programming by allowing the manipulation of the sequential order of gene activation for directing the differentiation of human stem cells.
One-sentence Summary: Development of a synthetic biology system for preprogrammed, stepwise activation of endogenous genes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429781 | PMC |
| http://dx.doi.org/10.1101/2024.09.17.613466 | DOI Listing |
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