Researchers invent new gene editing tool

Researchers from the University of Illinois, Chicago, have discovered a new gene editing technique that makes it possible to program sequential cuts – or modifications – over time.

CRISPR is a gene editing tool that enables scientists to change the DNA sequences in cells and sometimes add a desired sequence or genes. CRISPR uses an enzyme called Cas9 that acts like scissors to cut exactly at the desired location in the DNA. Once an incision is made, the ways in which cells repair DNA breakdown can be influenced to result in various changes or modifications to the DNA sequence.

The discovery of the no-till capability of the CRISPR system was described in the early 2010s. In just a few years, scientists have rejoiced at the ease of guiding CRISPR to target almost any DNA sequence in a cell or to focus on many different locations in a cell in a single experiment.

“A disadvantage of the currently available CRISPR-based editing systems is that all the edits or cuts are made simultaneously. There is no way to guide it so that it takes place sequentially,” Bradley of UIC said. Merrill, associate professor of biochemistry and molecular genetics at the College of Medicine and lead author of the article.

Merrill and colleagues’ new process involves the use of special molecules called guide RNA that transport the Cas9 enzyme within the cell and determine the exact DNA sequence against which Cas9 will cut. They call their specially designed guide RNA molecules “proGuides”, and the molecules allow the programmed sequential editing of DNA using Cas9.

Their findings are 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 be able to use the technique soon.

“The ability to pre-program the sequential activation of Cas9 across multiple sites provides a new tool for biological research and genetic engineering,” Merrill said. “The time factor is a critical component of human development and also disease progression, but the current methods of genetically examining these processes do not work effectively with the time element. Our system allows for no-till in a pre-programmed way, so researchers investigate the time-sensitive processes better, such as how cancer develops through single gene mutations and how the order in which the mutations occur can affect the disease. ‘