CRISPR gene editing just got a little more crisp

A new CRISPR system described this week in Cell has people wondering: how much better can this system get?

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Oct 01, 2015

Feng Zhang was one of the first researchers to have begun working on CRISPR-Cas9, one of the most exciting scientific tools since PCR, back in 2011. Four years later Zhang and his colleagues seem to have superseded this system with CRISPR-Cpf1.

CRISPR Cas9 exists as an adaptive immune system in prokaryotes where a bacterium targets invading viral DNA and cuts it with a Cas9-RNA complex, resulting in a double-stranded break with blunt ends. It was discovered that this system could be hacked to create cuts at targeted sites and either disrupt genes or insert new genetic material. While the blunt ends do not matter for a bacterium, whose only concern is to stop the virus, it is not the ideal situation for researchers looking to insert novel sequences at a targeted position in the genome.

The system described by Zhang and colleagues in the Cell paper is simpler in a number of ways:

  • Cas9 is guided by a pair of guide RNA molecules whereas Cpf1 only requires one RNA guide.
  • The cut performed by Cpf1 leaves the DNA cut with overhanging sticky ends; this makes it much easier to reliably insert a desired DNA sequence.
  • The Cpf1 enzyme is also smaller than Cas9, making it easier to insert into target cells.

The potential applications of CRISPR in various academic fields are broad and powerful. Creating knockdown model organisms could be made easier, as could processes in synthetic biology and gene therapy. Any increase in efficiency of the system could have a huge effect on industry and academic research.

One of the complications of the situation remains a tangled lawsuit between Broad Institute (MA, USA) and University of California, Berkeley (CA, USA) over the patenting of CRISPR-Cas9. Feng Zhang had originally patented the system, but the other pioneers of its use -Jennifer Doudna and Emmanuelle Charpentier- have disputed the patent. The dispute is hotly contested as the future of multi-million dollar companies and a potential Nobel Prize rests on the outcome.

It is likely that this new discovery will not put a stop to the patent dispute, but if the claimed benefits of Cpf1 are realized in its application, it may make the dispute over the now superseded Cas9 irrelevant.

The uptake of CRISPR-Cas9 by companies and universities alike was lightning fast. One paper on PubMed mentioned CRISPR-Cas9 in 2011. So far in 2015, 539 papers have mentioned it. With the diversity and ingenuity of evolution stumbling on solutions to viral infection, there are likely more enzymes out there which may improve the process still further. It is an exciting time in the history of genetics and genomics and observers are left to wonder: how much better can these new tools get?

– Written by Gerald Clarke

Source: Scientists discover new system for human genome editing with potential to increase power and precision of genome engineering

Originally published on GenomicsNet

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