Editing software for DNA

If you thought Photoshop was the cutting edge when it came to editing software, you ain’t seen nothing yet.

Spanish scientists have developed software that enables quick and easy deletion of DNA in living cells, turning the study of genomics into far more than a simple ‘ready only’ science. Their work has been published in the journal PLOS Computational Biology.

The scientists explained how the genome-editing technique CRISPR-Cas9 is typically employed in silencing protein-coding genes, the best-studied part of the human genome. However, the genome also consists of 99% of DNA that does not encode any protein — often described as the ‘dark matter’ of the genome — which is crucially important for understanding all aspects of human biology, including disease and evolution.

Researchers at Rory Johnson’s lab in the Barcelona Institute for Science and Technology (BIST) recently created a tool based on CRISPR-Cas9 called ‘DECKO’, which can be used to delete any desired piece of non-coding DNA. The method uses two individual single guide RNAs (sgRNAs), acting like two ‘molecular scissors’ that snip out a piece of DNA. Unfortunately, as no software was available for designing the pairs of sgRNAs that are required, designing deletion experiments was time-consuming.

In response to this, BIST researchers led by Carlos Pulido created a software pipeline called CRISPETa, a flexible solution for designing CRISPR deletion experiments. The user tells CRISPETa what region they wish to delete and the software returns a set of optimised pairs of sgRNAs that can directly be used by experimental researchers.

The researchers’ study shows that the software can create designs at high scales, with future screening experiments in mind. CRISPETa designs efficiently delete their desired targets in human cells. Importantly, in those regions that give rise to RNA molecules, the RNA molecules also carry the deletion.

The software is designed for use by non-experts so that it can be useful for scientific researchers, from even the most modest experimental laboratory. These users may, for example, delete a suspected functional region of non-coding DNA, and test the outcome on cellular or molecular activity. This software will also be potentially valuable for groups aiming to utilise CRISPR deletion for therapeutic purposes, eg, by deleting a region of non-coding DNA that is suspected to cause a disease state.

“Ultimately, we expect CRISPR deletion and other genome engineering tools to lead to a revolution in our ability to understand the genomic basis of disease, particularly in the 99% of DNA that does not encode proteins,” said Johnson.” Apart from being used as a basic research tool, CRISPR may even be used in the future as a powerful therapeutic to reverse disease-causing mutations.”

The software can be found at http://crispeta.crg.eu/.

Image caption: Deletion of genomic DNA by paired CRISPR. Cas9 proteins (scissors) are guided to their target sites by single guide RNAs (sgRNAs, orange ribbons). The target region in between is removed. CRISPETa software enables researchers to design such deletion experiments quickly and conveniently. Image courtesy of Pulido-Quetglas et al under CC BY 4.0