Scientists have identified a new CRISPR system for human genome editing with potential to increase power and precision of genome engineering.
The team including the scientist who first harnessed the revolutionary CRISPR-Cas9 system for mammalian genome editing, described the unexpected biological features of the new system and demonstrated that it can be engineered to edit the genomes of human cells.
"This has dramatic potential to advance genetic engineering," said Eric Lander, Director of the Broad Institute and one of the principal leaders of the human genome project.
"The paper not only reveals the function of a previously uncharacterised CRISPR system, but also shows that Cpf1 can be harnessed for human genome editing and has remarkable and powerful features," said Lander.
"The Cpf1 system represents a new generation of genome editing technology," said Lander.
Researchers searched through hundreds of CRISPR systems in different types of bacteria, searching for enzymes with useful properties that could be engineered for use in human cells.
Two promising candidates were the Cpf1 enzymes from bacterial species Acidaminococcus and Lachnospiraceae, which researchers showed can target genomic loci in human cells.
"We were thrilled to discover completely different CRISPR enzymes that can be harnessed for advancing research and human health," said Feng Zhang of Broad Institute.
The newly described Cpf1 system differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics, as well as for business and intellectual property.
In its natural form, the DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity.
The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues.
Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving 'blunt ends' that often undergo mutations as they are rejoined.
With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends.
This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more accurately.
Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be re-cut, allowing multiple opportunities for correct editing to occur.
The study was published in the journal Cell.