Micrograph of stem cell derived muscle cells.

CRISPR-Cas9 at the Crick

This year, Emmanuelle Charpentier and Jennifer Doudna became the first two women to share the Nobel Prize in Chemistry. Their ground-breaking research, developing a tool to edit DNA known as CRISPR-Cas9, has transformed biomedical science. They will receive their awards this week. To mark their achievements, we look at how genome editing is used by scientists across the Francis Crick Institute.

What is CRISPR-Cas9?

The CRISPR-Cas9 genome editing system is a tool used to edit sections of DNA. It includes two ingredients – Cas9, an enzyme that cuts DNA at a specific point, and a piece of genetic material called guide RNA. The guide RNA is designed to bind to a specific section of DNA, so directs Cas9 to the correct point to cut.

Once Cas9 has cut the DNA, the cell tries to repair itself and this is the point where researchers can change, add or remove genes. CRISPR-Cas9 is a fast, versatile and accurate method for genome editing.

With the advent of CRISPR-Cas9, scientists can now better alter the DNA of plants and animals, helping them to understand the causes of disease and even find potential new treatments. Cheaper than the tools scientists previously used, it has improved research in labs all over the world.

The Crick is no exception, with many of our researchers using a range of genome editing techniques including CRISPR Cas-9. In fact, 80% of our research groups use genome editing themselves or in collaboration with our specialist in-house experts.

“CRISPR has greatly changed the way my lab and many others work, making genetics faster, simpler and even more enjoyable,” explains Crick group leader Robin Lovell-Badge.

Tackling COVID-19

CRISPR has greatly changed the way my lab and many others work, making genetics faster, simpler and even more enjoyable.
Robin Lovell-Badge

Crick group leader Rupert Beale, an immunologist and clinical nephrologist, usually studies flu. But following the outbreak of SARS-CoV-2, the virus that causes COVID-19, he put his group’s normal research on hold. The lab members are experts in virology and they wanted to do all they could to help tackle the pandemic. With that in mind, Rupert and his team started trying to understand how the virus can replicate in human cells. 

Working with collaborators in Edinburgh at the Roslin Institute, the team is using CRISPR to identify the genes that are involved in virus replication. This involves performing a ‘knockout screen’ on the SARS-CoV-2 genome – blocking different genes one by one to find out which ones control the virus’ ability to multiply. The tool makes it much quicker for researchers to get a better understanding of this new virus and identify possible ways to stop it replicating. 

Translational research

Micrograph of stem cell derived muscle cells.

Muscle cells used to model laminopathies, with the characteristic deformed nuclei shown in green.

Daniel Moore is a Crick PhD student funded by Muscular Dystrophy UK. His work explores conditions called muscle laminopathies, particularly a severe type that affects children. The cells affected by laminopathies can be identified by their characteristic deformed nuclei. 

Daniel’s project uses patient induced pluripotent stem cells (iPSCs). iPSCs can be programmed to generate any cell in the body, and in Daniel’s project they are grown into tiny muscles that are used to model the disease. 

With the help of CRISPR, Daniel is correcting the affected gene in the mini-muscles and then checking to see if the genetic mutations in the nuclei have been corrected. Daniel aims to play a part in developing new gene therapies that correct the mutations that cause laminopathies, improving the lives of those affected by the diseases. 

Understanding parasite infection

Plasmodium falciparum is the deadliest parasite in humans and causes over 400,000 deaths each year through malaria. Toxoplasma gondii is less dangerous but infects up to a third of the world’s population. Usually the infection lies dormant, controlled by the immune system. But during pregnancy or when the immune system is suppressed, it can become a serious problem.

Moritz Treeck’s lab at the Crick is trying to find out how these parasites hide from the immune system, spread within the body and emerge to infect other people. Genome editing is a crucial tool to investigate how different genes in the parasites contribute to infection.

Heledd Davies and Joanna Young are postdocs in the lab, and CRISPR-Cas9 lets them quickly delete genes from the parasite and to establish their function.

Essential part of research

CRISPR-Cas9 has become an essential tool in biomedical research, and is a cost-effective technology with thousands of potential applications. Its recognition this year through the Nobel Prize shows how quickly it has transformed science.

“The Nobel announcement underscores the potential of CRISPR-Cas9,” says Crick group leader Kathy Niakan, who leads the Human Embryo and Stem Cell Laboratory. “If the UK can capitalise on this technology, with the advantage of the country’s regulatory rigour and scientific strengths, then it could strengthen its position as an international powerhouse in driving future scientific innovations”. 

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