A collaborative team of researchers from the Wellcome Trust Sanger Institute and the University of Cambridge has just described their recent work on generating a new CRISPR (clustered regularly interspaced short palindromic repeats) genome-editing platform that is freely available and works as a single-step system within every cell of the body and at every stage of development. The investigators are optimistic that this new approach will aid in the fields of developmental biology, tissue regeneration, and cancer.   

The U.K.-based teams developed two complementary methods—sOPiTKO, a knockout system that turns off genes by disrupting the DNA, and sOPTiKD, a knockdown system that silences the action of genes by disrupting the RNA. Using these two methods, scientists can inducibly turn off or silence genes in any cell type at any stage of a cell’s development from stem cell to fully differentiated adult cell. These systems will allow investigators to explore the changing role of genes rapidly and accurately as the cells develop into tissues such as liver, skin, or heart, and discover how this contributes to health and disease.

“As a cell develops from being stem cell to being a fully differentiated adult cell, the genes within it take on different roles,” explained co-senior study investigator Ludovic Vallier, Ph.D., senior group leader at the Wellcome Trust Sanger Institute and professor of regenerative medicine at the University of Cambridge. “Before, if we knocked out a gene, we could only see what effect this had at the very first step. By allowing the gene to operate during the cell’s development and then knocking it out with sOPTiKO at a later developmental step, we can investigate exactly what it is doing at that stage.”

The findings from this study were published recently in the journal Development in an article entitled “Optimized Inducible shRNA and CRISPR/Cas9 Platforms for In Vitro Studies of Human Development Using hPSCs.”