Two groups of scientists have unveiled a new and more precise arsenal of gene-editing techniques that could someday help us to eradicate genetic diseases with specifically targeted surgery at the chemical level.
New adaptations of the CRISPR-Cas9 gene-editing technique allow for single-letter changes in DNA base pairs and also provide the ability to edit individual RNA base pairs in human cells. Some have already called it ‘CRISPR 2.0’.
“We developed a new base editor, a molecular machine, which in a programmable, irreversible, efficient and clean way can correct mutations in the genome of living cells, “says David Liu, co-author of one of the papers.” When they go to specific sites in human genomic DNA, this conversion reverses the mutation that is associated with a particular disease, “he says.
Approximately half of the “point mutations” associated with human disease are confounded in the nucleobase pairs between the chemicals adenine (A), cytosine (C), guanine (G) and thymine (T), which constitute our DNA.
However, thanks to CRISPR-Cas9, scientists can alter genome structures with a technique that effectively cuts, copies, and pastes the molecular arrangements of these base pairs, but so far, the technique could not change pairs of individual DNA bases.
One of the new tools, developed by Liu’s team, called the Adenine Base Editor (ABE) changes this, making possible much clearer editions, rearranging the adenine atoms to resemble guanine (G), causing the AT base pairs become GCs.
Despite what it may seem, of the 32,000 point mutations we know to be linked to the disease, about half could be resolved through that single exchange.
By combining it with other basic editing systems, this discovery could help us repair nearly two-thirds of all disease- causing mutations.
In a second separate but related study published in Science, another team at the Broad Institute details the development of Cas13, a CRISPR protein that makes RNA editing possible.
Unlike DNA editing, which makes permanent changes in the structure of the genome by rearranging nucleobases, editing RNA is a lighter and non-permanent technique, in this case possible thanks to another precise change: the change from adenosine to inosine, which is interpreted in cells such as guanine.
In cells, RNA acts as a kind of messenger that helps regulate the way our genes produce proteins.
“So far, we have become very good at gene deactivation, but actually regaining the function of lost proteins is much more challenging,” explains Feng Zhang, principal investigator of this second work.
“This new ability to edit RNA opens up more potential opportunities to recover that function and treat many diseases, in almost any cell type,” says Zhang.
When will it be available?
The truth is that it will be some time before any of these new genetic editing systems come to help patients in clinical situations, because even if the technology already exists, we will not know how reliable, safe and effective these methods are until further research is carried out.
Undoubtedly, both are incredibly promising developments in the health sciences, and someday they could be used to treat conditions such as genetic blindness, metabolic disorders, Parkinson’s disease and many more.