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New CRISPR technique could improve precision

5 October 2015
Appeared in BioNews 822

Scientists have identified a new version of the gene-editing technique CRISPR, which could enable greater precision in the editing of genomes, while making its use simpler and more flexible.

Researchers led by one of the scientists involved in developing the CRISPR/Cas9 technique, Professor Feng Zhang of the Broad Institute at MIT and Harvard in Cambridge, Massachusetts, described a protein called Cpf1, which is not only capable of editing the human genome, but also possesses a host of unique features that could have important implications for research.

'This [study] has dramatic potential to advance genetic engineering,' said Dr Eric Lander, director of the Broad Institute. '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.'

The traditional CRISPR/Cas9 system relies on the Cas9 molecular 'scissors' to make precise snips in a particular region of DNA, which is identified by two RNA guides. The DNA sequence at these snips can then be deleted or replaced, but the technique has some limitations and Professor Zhang and his team sought out a simpler and more precise method.

In a search for Cas9-like proteins, the researchers combed through genomes of several bacterial species and found two species harboring Cpf1 enzymes that were proficient at human genome editing.

Being a smaller protein, Cpf1would theoretically be better tolerated by certain cell types. Furthermore, it only needs a single, short RNA molecule to be directed to its destination in the genome. These destinations, too, are defined by a different set of sequences, opening up the possibility of editing genomes that proved intractable by Cas9.

Perhaps most importantly, while Cas9 cuts straight across the two DNA strands, Cpf1 makes staggered cuts, creating 'sticky ends'. These could provide more efficient, error-free replacements of DNA sequences. 'The sticky ends carry information that can direct the insertion of the DNA. It makes the insertion much more controllable,' said Professor Zhang to Nature News.

It is likely that more CRISPR systems exist in nature, as they are a part of bacterial defence systems against viruses. 'I can't even begin to count how many there may be. There really is great diversity that we as a scientific community should go out and explore,' Professor Zhang told The Economist.

The Progress Educational Trust's public conference 'From Three-Person IVF to Genome Editing: The Science and Ethics of Engineering the Embryo' is taking place in central London on Wednesday 9 December 2015. Find out more here.

Alternative CRISPR system could improve genome editing
Nature |  10/15
Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System
Cell |  25 September 2015
The Economist |  3 October 2015
New CRISPR/Cpf1 Genome Editing System Makes Waves at CSHL Meeting
Genomeweb |  28 September 2015
Scientists discover new system for human genome editing
Eurekalert (press release) |  25 September 2015
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