Scientists at ETH Zurich have developed a process using CRIPS-Cas for editing hundreds of genetic sites within cells at the same time.

The advent of CRISPR (clustered regularly interspaced short palindromic repeats) gene-editing technology has had a significant impact on both genetic research and the development of new gene and cell therapies. The technology has been used to delete, replace or modify genes in cells, as well as to upregulate or downregulate gene activity. Most often, just one gene has been modified at a time, although occasionally a few have been edited at once.

That may change, however. Researchers at the Department of Biosystems Science and Engineering at ETH Zurich in Basel have developed a process that could allow CRISPR-Cas editing of up to hundreds of genes at one time. The researchers have demonstrated that the process can be used to simultaneously edit 25 target sites.

Their approach involved the creation of a plasmid (circular DNA) that stores the direction for the production of the Cas12a enzyme and various RNA directing molecules in sequences. Inserting the plasmid into cells results in simultaneous modification and regulation of the multiple genes targeted by the RNA molecules, because the Cas12a enzyme not only edits genes, but also cuts the sequence of RNA addresses into individual addresses. The Cas12a enzyme also functions with shorter RNA directing molecules compared to the more commonly used Cas9 enzyme.

With the new process, entire gene networks can be modified systematically in a single step, providing the potential for complex, large-scale cell programming. Potential applications include an investigation into why certain types of cells behave the way they do, converting stem cells into differentiated cells, for eventual use in cell therapies.