In 2012, Thorsten Stafforst and his team at the university of Tubingen discovered a method of altering the sequences of messenger RNA, the molecule that bridges the gap between DNA and protein synthesis. Despite the potential of this technique to treat diseases by altering protein production, the discovery was overshadowed by that of CRISPR-Cas9, a DNA editing tool that makes changes to the genome itself.
While CRISPR has been revolutionary, its use as a therapeutic technique has proven problematic, leading to newfound interest in RNA editing.
Researchers have documented ways that Cas9, one of the enzymes used in CRISPR gene editing, could trigger immune responses, or cause accidental changes to the genome that would be permanent. RNA editing, by contrast, could allow clinicians to make temporary fixes that eliminate mutations in proteins, halt their production or change the way that they work in specific organs and tissues. Because cells quickly degrade unused RNAs, any errors introduced by a therapy would be washed out, rather than staying with a person forever.Nature – Step aside CRISPR, RNA editing is taking off. (2020).
Retrieved 5 February 2020, from https://www.nature.com/articles/d41586-020-00272-5
Use of RNA editing has shown some promise in the lab. For example, a study published last year showed that in mouse models of muscular dystrophy, RNA editing could restore the dystrophin protein to 5% of its normal levels, enough to have therapeutic benefits.
RNA editing currently has significant limitations, however. While CRISPR cuts the DNA strand to remove or insert new sequences, current RNA-editing proteins are only able to change the letters (bases) that form the genetic code.
Research is currently underway to expand RNA-editing capabilities, for example by altering RNA-editing proteins to exchange different bases.
Step aside CRISPR, RNA editing is taking off: https://www.nature.com/articles/d41586-020-00272-5#ref-CR6
In vivo RNA editing of point mutations via RNA-guided adenosine deaminases: https://doi.org/10.1038/s41592-019-0323-0
A cytosine deaminase for programmable single-base RNA editing: https://doi.org/10.1126/science.aax7063