Upgraded CRISPR edits thousands of genes at once

An upgraded version of the CRISPR approach to genome editing has been used for the first time to edit multiple genes at once and assess the effects of editing.

It is hoped that this advance will make it easier for scientists to identify pathological genetic changes in the future.

'For several years, scientists have used CRISPR to cut many genes at one time. But there was a lack of CRISPR methods to edit many genes at once,' said Dr Leonid Kruglyak, senior study author, at the University of California, Los Angeles (UCLA). 'Our lab is the first to develop a large-scale technique for achieving this in cells structured like human cells.'

The study, published in Nature Genetics, used an updated version of CRISPR/Cas9 to rapidly assess the outcome of genome editing for thousands of genes at once. With previous technology it was also possible to cut many genes at the same time but a significant challenge was to subsequently edit these genes correctly, and avoid these cut-up genes matching up incorrectly after cutting.

The updated system addresses this issue as it uses so-called RNA guides that are physically attached to the DNA, which ensures correct coupling of the DNA patches.

Another challenge was that effects of genome-edits had to be assessed individually, making this process time-consuming. In this study, thousands of mutations were introduced in different yeast cells simultaneously, making it possible to observe effects of individual mutations in cells.

The CRISPR/Cas9 gene editing approach was first developed in 2012 and is based on a simple bacterial immune system.

The researchers hope that the current advance can be used to establish whether unknown mutations will have adverse effects in an individual.

'We can now edit the genome in thousands of different ways, while observing positive or negative effects on cells. Our ultimate goal is to help scientists zero in on the genetic culprit for a disease, leading to doctors to a firm diagnosis and allowing patients to obtain the most effective treatment,' said Dr Kruglyak.