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CRISPR: pinpointing the causes of blood cancer

The Bloodwise logo. Bloodwise appears in black text against a white background
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11 May 2016

Today we wanted to talk about a technique that’s sweeping across the global scientific community, polarising ethical debates - yet in reality is just a tiny pair of biological molecules that form a part of the bacterial immune system. This scientific revolution is due to a small piece of genetic information, known simply as CRISPR (or by the significantly less pronounceable Clustered Regularly Interspaced Short Palindromic Repeats).

The reason for the rise of CRISPR is simple: the ability to quickly and efficiently edit the human genome represented one of the major ambitions of scientists in both the 20th and 21st centuries. For decades researchers scavenged the sub-cellular world to uncover biological tools with the capacity to remove genetic deficiencies that underlie human diseases. CRISPR has now emerged as the technology that can do this and do it well.

Discovered in 2012, the CRISPR gene editing system has surprised the research community with the ease and accuracy by which it can be tailored to manipulate genomes across many species. In the laboratory, such changes were first made in bacteria, followed soon by mice and then, by 2013, DNA was successfully cut from human stem cells. These results categorically demonstrated that CRISPR lived up to expectations; precise alterations to the human genome were possible.

On the back of this significant breakthrough, various ethical summits were quickly arranged to discuss the implications of CRISPR. As it stands, no country possesses legislation permitting CRISPR edits to the genetic code that eggs or sperm are derived from (the ‘germline’) in a way that could pass between generations.

Whether any countries plan to make moves towards change remains unclear, yet heated debate continues between scientists, policy makers and philosophers across these international congresses. What is apparent, however, is that CRISPR has established the foundations of a possible medical revolution.

How CRISPR works and how blood cancer researchers use it

If we begin with the fundamentals, CRISPR are short lengths of DNA that form part of the bacterial immune system. When infected with a pathogen, such as a virus, enzymes of the bacterial cell recognise and cut out parts of the foreign DNA, storing it within their own DNA helix – this is a CRISPR sequence.

This is how bacteria create an immune memory of infection. Upon reinfection, the cell uses the deposited CRISPR sequence as a homing device to lock back on to the corresponding DNA of the intruder and, through cooperation with an enzyme called CAS9, cuts it in half, killing the pathogen.

Researchers use CRISPR by first taking both a CRISPR sequence and CAS9 enzyme out of bacterial cells. Using a well-established approach, the CRISPR code can be changed in the lab and genetic information, taken from any organism, is inserted in place of the original sequence.

When this artificial CRISPR is then put inside a cell from the organism of interest alongside CAS9, it acts just like there's a virus invading a bacterial cell. It binds to the target site within the organism’s DNA, believing it to be foreign, and the CAS9 enzyme cuts the gene in middle of this sequence, rendering it dysfunctional. The method is therefore quite simple: we steal the DNA-slicing defensive system of a bacterium to target a gene of our choice.

The CRISPR system also allows researchers to render the 'cutting' function of CAS9 inactive. With a few clever tweaks, the attachment of CRISPR and CAS9 can be made to activate the target gene instead of chopping it up, or to make small tweaks to the sequence of DNA letters. This flexibility highlights yet another reason why this technology is such a useful tool for manipulating the genome.



Despite the media and ethical furore, the actual impact of CRISPR to-date has mainly been restricted to the lab.

Accurately editing parts of the genome hasn’t always been easy and scientists have been quick to exploit CRISPR’s natural propensity to do so. Researchers across the globe are quickly mastering this flexible technology, replacing laborious genetic engineering tools with one that can manipulate DNA at unprecedented scale and speed, and accelerating our fundamental understanding of how genes normally work and how they can go awry in disease.

As well as an extraordinary useful lab tool, researchers are also thinking about potential treatment targets in their speciality areas, ranging from cancers to visual disorders.

CRISPR in blood cancer and at Bloodwise

The hope for CRISPR is that it can be harnessed successfully in future to correct genetic defects that underlie diseases such as blood cancers. Cancers develop due to genetic faults, known as mutations, and therefore represent possible targets for gene therapy approaches.

Although we aren’t yet close to bringing this technology directly into humans, one Bloodwise-supported researcher, Professor Jacqueline Boultwood at Oxford, is using CRISPR to alter the function of genes that appear to be risk factors for chronic myeloid leukaemia (CML) and myelodysplastic syndromes (MDS)

By turning different genetic targets on or off, this research is pinpointing exactly which of these are critical for the cancer to emerge, proliferate and evade treatment. Results so far have been very enlightening: CRISPR-mediated changes were successfully made to a specific gene (ASXL1) in cancerous CML cells grown in the lab. When these cells were then transplanted into mice, animals receiving the CRISPR-transformed tissue survived longer, appearing to render the cancer less aggressive.

Professor Boultwood is also developing the use of CRISPR in her lab to correct cancerous stem cells that drive other blood disorders with a particular focus on myelodysplastic syndromes (MDS). These genetic corrections would only be made to the patient’s own stem cells, so wouldn’t be passed on to future generations, but could offer exciting new treatment opportunities if successful. We have committed £239,000 to this CRISPR-specific project led by Professor Boultwood plus, acorss the UK, we are investing over £3 million and £9 million towards wider research into CML and MDS repsectively.

Further reading

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