New CRISPR protein could drastically improve genetic editing

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Researchers have identified a new protein with the CRISPR system for slicing DNA, which could allow scientists to begin editing the human genome with great precision.

Researchers trying to improve methods for editing the human genome have identified a new CRISPR system that has the potential to increase the precision and power of genetic engineering. According to a report from Business Standard, the team working on the new developments even included the scientist that first discovered the power of the CRISPR-Cas9 system for editing mammalian genomes.

The study described some unexpected biological attributes of the new system for editing genomes, showing how it can be engineered to alter the DNA inside of human cells. It could have widespread implications throughout the healthcare field. Eric Lander, the Director of the Broad Institute and one of the leaders of the human genome project thinks that the development has the potential to shoot the field of genetic engineering into the stratosphere.

“The paper not only reveals the function of a previously uncharacterized CRISPR system, but also shows that Cpf1 can be harnessed for human genome editing and has remarkable and powerful features,” Lander said.

The Cpf1 system is the absolute latest in technology for genome editing. Scientists tested hundreds of different CRISPR systems in different strains of bacteria, looking for enzymes that could be incorporated with systems used to edit human cells. Two of the most promising strains carried Cpf1 enzymes that would incorporate into human cells, Acidaminococcus and Lachnospiraceae. The scientists on the research teams that discovered the new methods were thrilled by the discovery, projecting that the new method will significantly improve current genomic engineering models.

The newly discovered system is different from the previously used method to edit human genomes, Cas9 for several reasons. It has huge implications for therapies and research, and could be a turning point in many businesses and intellectual property cases.

The DNA-slicing enzyme Cas9 acts a pair of scissors, connecting with two small RNA molecules to slice up genetic information and reassemble it in different orders. The new system, using the enzyme Cpf1 is much simpler in that it only uses one RNA molecule. The Cpf1 enzyme is much smaller than the previously used SpCas9 enzyme which makes it much easier to deliver into cells and tissues.

Cpf1 also approaches the task of splitting DNA differently than Cas9. When Cas9 cuts DNA, it splits both strands of the molecule in at the same place, leaving blunt ends behind that are subject to mutations upon being reconnected. Cpf1, on the other hand, cuts the DNA molecules in an offset fashion, leaving short overhanging edges on the sliced ends.

The new method will help improve precision while slicing DNA, which will allow researchers to more accurately pair strands to produce desired genetic effects. Cpf1 makes cuts far away from the DNA’s recognition site, which allows doctors to be able to correct mutations should one occur by simply re-cutting the molecule.

The study was published in the journal Cell, and has serious implications for the field of human genetic engineering. The new Cpf1 protein was discovered at a time when the CRISPR/Cas9 method was showing up in labs across the entire world. Rival scientists continue to fight over the patents to the genome-editing tool, each claiming to be the first one to have developed the technology.

The new protein will likely prove to be much more effective at the precision editing many researchers are striving towards, and there is a good chance that there are even more effective proteins that still have not been discovered yet. CRISPR sequences are actually a prehistoric method of slicing and reassembling genetic information that have been passed down by bacterial strains for billions of years.

According to John van der Oost, a microbiologist from Wageningen University and co-author of the paper, “There are definitely many more defense systems out there, and maybe some of them might even have spectacular applications like with the Cas9 system. We have this feeling it’s just the tip of the ice berg.”

The initial discovery of CRISPr/Cas9 and its usefulness in editing genes was not intentional, and was made by scientists researching the DNA of different strains of bacteria. They noticed clustered groups of the same repeating sequences, and realized that the bacteria were actually using a primitive immune system to scan their DNA for viruses and remove them if necessary. The spaces between repeated sequences are actually little bits of virus DNA, and the proteins associated with the CRISPR system identify these profiles and destroy their DNA.

Cas9 was discovered as a useful gene-editing tool when Emmanuelle Charpentier, a researcher studying the flesh-eating microbe Streptococcus pyogenes, accidentally revealed the protein’s special abilities. The bacteria in her samples were observed carrying out Cas9 proteins, which were able to cut the DNA based on an RNA guide sequence with great precision. In 2012, Charpentier and biologist Jennifer Doudna from UC Berkeley published a paper outlining their findings on the CRISPR/Cas9 system, and have been embroiled in a legal battle ever since over the rights to the genome-editing tool with another Harvard research team that claims to have discovered it first.

While it may be some time before doctors will be able program traits in a human being, the discovery of the new protein could mean that great leaps forward in the field of genetic engineering are on the horizon.

Wanda B. Hewlett

Wanda B. Hewlett (Contributor) is a freelance writer from the UK. When she’s not busy writing she loves to spend her time traveling, exploring and running.

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