For the first time, scientists used a controversial gene-editing technique called base editing to correct a gene mutation in human embryos linked to the hereditary blood disorder beta thalassemia, according to the study published in the journal Protein & Cell in September.
A change to a single base pair in your genetic code, known as a point mutation, can cause beta thalassemia.
The scientists noted that the efficiency of repairing mutations in the study was only about 20% — so they were not 100% successful in effectively editing all of the embryos all of the time. Yet the study findings and the base editing technique are now gaining international attention.
The base editor technique is similar to the powerful gene-editing tool called CRISPR, but there is a major difference.
Base editing uses some of the components of CRISPR, but directly makes changes to a targeted site in DNA without cutting the DNA, said David Liu, core institute member of the Broad Institute and professor of chemistry and chemical biology at Harvard University, who was not involved in the study.
When a cut is made in genomic DNA using the traditional CRISPR approach — for instance, to disrupt a mutation — the primary response of a cell is to repair the cut and, in the process, disrupt the DNA at the cut site, Liu said.
“But many human genetic diseases are caused by single point mutations that need to be precisely corrected, rather than disrupted, in order to treat or study the corresponding disease,” Liu said. That’s where base editing comes in.
“Base editing, in contrast, does not make a double-stranded cut in the target DNA. Instead, base editors directly perform ‘chemical surgery’ on the target DNA base to convert one base pair to a different base pair, that is, to make a point mutation,” said Liu, whose research group at Harvard developed base editing.
“It’s important to note that compared to traditional nuclease-mediated genome editing methods such as the use of CRISPR-Cas9, base editing is a complementary — not necessarily better — approach, and each approach has its strengths and preferred applications,” he said.
About two-thirds of known human genetic variants associated with diseases are point mutations, so base editing has the potential to correct or reproduce such mutations for research purposes, Liu said.