Researchers have discovered a new kind of enzyme that could open the door to even more efficient and accurate gene-editing in this rapidly developing field.
The enzyme could be deployed within the CRISPR (clustered regularly interspaced palindromic repeats) gene-editing system in mammals. CRISPR, introduced in 2012, propelled forward genetic research because the method made it significantly cheaper and easier to cut and paste sections of DNA.
“This has dramatic potential to advance genetic engineering,” Eric Lander, Director of the Broad Institute, said in a statement.
CRISPR is a sequence of genes, found naturally in bacteria, that function as a database for its immune system, cataloging different viruses and supplying that information for enzymes, which attack the invading viruses by chopping up their DNA. Since 2012, scientists have harnessed CRISPR as a gene-editing tool and used it to make insertions and deletions in human DNA, mostly in the search for treatments for gene-based diseases.
The sole enzyme available to scientists using CRISPR was Cas9—the gene-editing system was commonly known as CRISPR/Cas—until now. On Sept. 25, Feng Zhang and his fellow researchers at the Broad Institute published their study of how the Cpf1 enzyme could serve as a better editing tool than the Cas9.
“The Cpf1 system represents a new generation of genome editing technology,” said Lander.
The controversial side to the accessibility of gene-editing is the ease with which the technology can be deployed for research in ethically grey areas, such as human enhancement. In North America and Western Europe, the consensus among biologists is that gene-editing should be restricted to somatic cells until the full ramifications of modifying germline (embryonic) cells are explored in theory.
In April, Chinese researchers provoked a furor in the research community with the publication of research that included the editing of the genomes of human embryos. The embryos were never viable, but the study still drew admonishment, directly and indirectly, from the research community.
The Cpf1 was found after Zhang and his colleagues looked at CRISPR systems in hundreds of different kinds of bacteria for enzymes that could be modified for editing human cells, and claims it has several advantages over Cas9.
First, the Cpf1 is composed of only a single Ribonucleic acid (RNA) instead of two like the Cas9, and the individual Cpf1 RNA is smaller than its Cas9 counterpart, making it easier to insert into the targeted cells.
Second, the Cas9 cuts both DNA strands in the same place, leaving “blunt ends” that can suffer mutations when they’re rejoined. Cpf1 enzymes leave offsets, enabling more precise insertions and more efficient integration of DNA.
Third, the Cpf1 makes cuts far away from the recognition sequence in the DNA, so that even if mutations occur at the location where the cut was made, re-cuts can happen later, allowing for corrections to be made in the editing process.
Zhang and the Broad institute plan to make the technology freely available for academic research, as it had done with Cas9 reagents Zhang’s lab had discovered. Zhang said that his goal was to develop tools that can accelerate research in gene-editing, and expects more relevant enzymes to be discovered going forward.