A new gene editing tool allows you to program sequential sections over time

Researchers at the University of Illinois at Chicago have discovered a new gene editing technique that allows programming sequential slices – or edits – over time.

CRISPR is a gene editing tool that allows scientists to modify DNA sequences in cells and sometimes add the desired sequence or genes. CRISPR uses an enzyme called Cas9 that acts like scissors to cut exactly where you want it in DNA. Once an incision is made, the ways in which cells repair DNA breakdown can be influenced to result in various changes or edits to the DNA sequence.

The discovery of the ability to edit the genes of the CRISPR system was described in early 2010. In just a few years, scientists have fallen in love with the ease of directing CRISPR to target almost any DNA sequence in a cell or to target many different sites in a cell in a single experiment.

“The disadvantage of currently available CRISPR-based editing systems is that all edits or cuts are made at once. There is no way to run them in a row, one after the other,” said Bradley of the UIC. Merrill, Associate Professor of Biochemistry and Molecular Genetics at the School of Medicine and lead author.

A new process by Merrill and colleagues involves the use of special molecules called RNA that guides the fermenting enzyme Cas9 inside the cell and determining the exact DNA sequence on which Cas9 will be cut. They call their specially designed hydrogen RNA molecules “proGuides,” and the molecules enable programmed sequential DNA editing using Cas9.

Their findings were published in the journal Molecular cell.

While proGuide is still in the prototype phase, Merrill and colleagues plan to further develop their concept and hope that researchers will soon be able to use the technique.

“The ability to pre-program Cas9 sequential activation across multiple locations introduces a new tool for biological research and genetic engineering,” Merrill said. “The time factor is a critical component of human development and disease progression, but current methods for genetic research of these processes do not work effectively with the time element. Our system allows gene editing in a pre-programmed way, allowing researchers to better investigate time-sensitive processes such as cancer development from several gene mutations and how the order in which these mutations occur can affect the disease. “


University of Illinois at Chicago

Journal reference:

Clarke, R., and others. (2020) Sequential activation of RNA guides to enable sequential CRISPR-Cas9 activities. Molecular cell. doi.org/10.1016/j.molcel.2020.12.003.