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MIT CRISPR team turn to RNA

6 June 2016
Appeared in BioNews 854

The team that developed the CRISPR/Cas9 DNA-editing technique have now developed a new system that could allow RNA editing.

An RNA-editing system is potentially more versatile than its DNA counterpart when developing treatments for genetic diseases, cancer and infectious diseases. The system could also improve scientific understanding of how RNA works in cells.

The CRISPR/Cas9 DNA-editing system is based on a natural defence mechanism that evolved in bacteria to protect against viruses. Researchers led by Dr Feng Zhang at the Broad Institute of MIT and Harvard describe how they found an analogous enzyme, called C2c2, in the bacterium Leptotrichia shahii, which naturally targets RNA as part of that bacterium's immune system.

'Nature has already invented all these really interesting mechanisms. We're just trying to play with that and learn how they work, then turn them into tools that will be useful to us,' said Dr Zhang.

In living cells, DNA gets transcribed into RNA, which is then translated into proteins by cell structures called ribosomes. But recent research suggests that RNA may play a more important role than simply carrying out the instructions contained in the cell's DNA, and abnormal levels of certain RNAs have been observed in heart disease and some cancers.

Reporting the team's findings in Science, Dr Zhang described how they inserted C2c2 into another species of bacteria, where it was able to alter levels of single-stranded RNA. They were able to reduce the expression of the gene encoded by the RNA, which suggests that it may eventually be possible to turn down levels of gene expression rather than simply silencing genes.

'The problem with DNA editing is that it's permanent. DNA repair mechanisms are so strong that it may be more effective to act on the RNA rather that cutting the DNA,' said Dr Gene Yeo of the Institute of Genomic Medicine at the University of California, San Diego. 

Last year, their rival team at the University of California, Berkeley – led by Professor Jennifer Doudna – used a different approach to modify the CRISPR/Cas9 system to edit RNA rather than DNA. The two teams are currently in a patent dispute over the CRISPR technology itself (see BioNews 835).

The C2c2 system has not yet been tested in mammalian cells, but Professor Zhang says he is confident that this will be possible, and he believes that it is likely to be more effective than Professor Doudna's system because it is a based on a natural RNA-targeting system rather than an engineered one.

'RNA is the blueprint through which genes regulate cellular processes,' Dr Oliver Rackham of the University of Western Australia, who was not involved in the study, told New Scientist. 'The exciting thing about this study is that it now opens up the RNA world to the ease of experimental design afforded by CRISPR.'

A CRISPR system for editing RNA
Eurekalert (press release) |  2 June 2016
Bacterial RNA-editing tool could disable viruses or halt disease
New Scientist |  2 June 2016
C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector
Science |  2 June 2016
New CRISPR system for targeting RNA
MIT News (Broad Institute press release) |  2 June 2016
RNA-Targeting CRISPR
The Scientist |  2 June 2016
Taking Gene-Editing to the Next Level
Scientific American |  2 June 2016
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