1 June 2017

Researchers decipher how a new molecular tool edits your genome

Gene editing

A new protein of the CRISPR-Cas family upgrades the possibilities for genome modification a la carte, such as genetic damage repair and other biomedical or biotechnological applications. The protein could be used to repair or activate specific DNA regions in the genome.

Proteins that can find and cleave DNA – and target specific sites of the genome have been in high demand among scientists ever since we first mapped the human genome. Now, researchers from Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen (UCPH) have published an article in Nature that unveils the working mechanism of a new protein, Cpf1. This protein contains an internal GPS to find specific genes to carry out ‘a la carte’ genome modification and repair DNA lesions.

”I believe that this discovery will allow us to edit the instructions contained in the genome. By editing the instructions, we will be capable of developing genetically-modified organisms or treat genetic diseases,” says the leader of the study Professor Guillermo Montoya from the Novo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences.

A molecular GPS
The study reveals how Cpf1, this new molecular tool for genome editing, unwinds and cleaves the DNA to initiate the gene modification process. With this new tool the genome is ‘cut’ in a way that creates sticky ends instead of the blunt end that is generated by today’s most popular tool for gene modification, Cas9. Another important advantage of this precision tool is that it will only cut the desired DNA sequence and not cut in any other locations of the genome.

“The high accuracy enables the Cpf1 to act like a GPS with the ability to identify its destination within the intricate map of the genome. Cpf1 is extremely adaptable and can easily be reprogrammed compared to the more complex CRISPR proteins,” explains Guillermo Montoya.

The structure of Cpf1 unveils how this protein recognises and cleaves the DNA to initiate the editing process.

Stefano Stella and Pablo Alcón in Professor Montoya’s research team at CPR have solved the three-dimensional structure of the protein using X-ray crystallography. Solving the structure gives us insights into how this protein recognizes and unzips the target DNA to start the genome modification process. This information is key to engineer this genome modifying tool.

The article 'Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage' has just been published in the scientific journal Nature.

Professor Guillermo Montoya
Email: guillermo.montoya@cpr.ku.dk
Phone: +45 35 33 06 63 / Mobile: +45 51 32 45 81