Over the past 3 years, a method called CRISPR (clustered regularly interspaced short palindromic repeats) has made editing genes a whole lot easier. It has given researchers faster or simpler ways to modify the DNA of crops and animals, conduct biomedical experiments, and, most controversially, genetically engineer human embryos. But the technique is about to get even better, according to a new study. A research team has found a new bacterial protein that effectively makes CRISPR’s DNA scalpel sharper, and thus could make gene editing even easier and cheaper.
CRISPR is the result of a billions-year battle between bacteria and the viruses that infect them. Over the past decade, microbiologists have discovered that microbes have many ways to identify viral genetic material that has gotten into their DNA and cut that DNA out. The microbes typically depend on a complex that includes a DNA-cutting protein attached to RNA that helps guide this protein to its genetic target. Many of these complexes have proven quite complicated, but scientists have put those involving a protein called Cas9 to use: deleting, modifying, and even adding DNA to organisms ranging from yeast to humans.
Yet even as teams developed the CRISPR/Cas9 gene-editing system for biomedical and basic research purposes, multiple groups have been on the lookout for better versions of the molecular scalpel.
Feng Zhang's team may have won the initial race. A molecular biologist at the Broad Institute and the McGovern Institute for Brain Research at Massachusetts Institute of Technology in Cambridge, Zhang and colleagues have screened hundreds of candidate enzymes, among them, a protein called CPF1 that’s used by many different types of bacteria to fight off viruses. CPF1 from two of these bacteria were able to edit DNA in human cells, Zhang’s team reports online today in Cell.
Among their advantages over Cas9, Zhang says, is that the CPF1s require a smaller helper RNA—small enough that the RNA will be much easier and less costly to make. It has other potential advantages that may enable more precise editing of more places in a genome.
For example, CPF1 cuts DNA differently, so the two strands at the end of a cut piece of DNA are of uneven lengths instead of the same lengths as with Cas9, which Zhang says is a potential advantage for making specific gene changes. It's still unclear whether CPF1 will be better than Cas9 in the long run, says Rodolphe Barrangou, a molecular biologist at North Carolina State University in Raleigh, who was not involved in the work. Regardless, "It's a noteworthy addition to the biology [of CRISPR] and a valuable addition to the tool box."
And Zhang is still looking for other DNA scalpels. "I think there are many, many other ones out there," he says.