Two groups of scientists have revealed a new and more precise arsenal of gene editing techniques that could one day help us eradicate genetic diseases with chemically targeted surgery.
New adaptations of the CRISPR-Cas9 gene editing technique allow 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”, comments David Liu, co-author of one of the papers. “When they target certain sites in human genomic DNA, this conversion reverses the mutation that is associated with a particular disease,” he clarifies.
About half of the “point mutations” associated with human disease are confused in the nucleobase pairs between the chemicals adenine (A), cytosine (C), guanine (G), and thymine (T), which make up 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 until now, the technique could not change the pairs of individual DNA bases.
One of the new tools, developed by Liu’s team, called Adenine Base Editor (ABE) changes this, making much sharper edits possible, rearranging adenine atoms to resemble guanine (G), causing them to base pairs AT become GC.
Despite what it may seem, of the 32,000 point mutations that we know to be linked to the disease, about half could be resolved through that unique exchange.
When combined 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 from 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, RNA editing 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 as guanine.
In cells, RNA acts as a type of messenger that helps regulate the way our genes make proteins.
“ So far, we’ve gotten very good at knocking out genes, but actually recovering lost protein function is much more challenging, ” explains Feng Zhang, principal investigator on this second work.
“This new ability to edit RNA opens up more potential opportunities to regain 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 gene editing systems come to help patients in clinical situations, since, although the technology already exists, we will not know how reliable, safe and effective these methods are until further investigation is carried out.
Undoubtedly, both are incredibly promising developments in the health sciences, and could one day be used to treat conditions such as genetic blindness, metabolic disorders, Parkinson’s disease, and many more.
Reference: DBT Cox; JS Gootenberg; OO Abudayyeh; B. Franklin; MJ Kellner; J. Joung; F. Zhang. ‘RNA editing with CRISPR-Cas13’. Science 2017 science.sciencemag.org/lookup/doi/10.1126/science.aaq0180
David Liu et al .: ‘Programmable base editing of A • T to G • C in genomic DNA without DNA cleavage’. Nature, 2017. nature.com/articles/doi:10.1038/nature24644
