Novel gene editing has gained some attention of recent, with clinical trials using CRISPR to battle the likes of cancer and neurological diseases, making headlines. With former Facebook president Sean Parker funding a $250 million foundation aimed at CRISPR in the treatment of cancer, it would be modest to say that scientists have high hopes for a success.


What is CRISPR Gene Editing?  

  • Clustered Regulatory Interspaced Short Palindromic Repeats
  • CRISPR complex is comprised of the Cas9 enzyme and ‘guide’ RNA which is administrated to the patient’s target cells (with cancer, the target cells will depend on the cancer type)
  • The guide RNA essentially ‘guides’ the Cas9 enzyme to the defective DNA which is causing disease. The guide RNA’s sequence is complementary to the defective DNA and is able to bind
  • Cas9 is an active enzyme, able to unzip and unwind the double helical structure of DNA, stretching out the DNA strands
  • The defective target DNA is now cut by Cas9 and can now be repaired by the body’s own DNA repair mechanisms
  • As a result, CRISPR is able to edit the DNA molecule, which will code for a different protein and will no longer be disease-causing, so can be used in curing a patient’s cancer. CRISPR essentially is curing the ‘faulty’ genes that cause cancer.


Source: Cancer Research UK


How is CRISPR administered to the patient?

Contrasting with the typical oral and IV (injection) administration of conventional chemotherapy, which is highly off-target, most of which target rapidly dividing cells including our normal, rapidly dividing cells of the gastrointestinal tract (inducing nausea and vomiting) and hair cells (associated with hair loss); CRISPR can be administrated to the patient in two ways.

  1. Ex vivo (outside body). Cells are removed from the patient, delivered the CRISPR/ Cas9 complex and grown in the lab, causing the desired outcome of DNA editing and repair. The successfully modified cells are expanded in culture and returned to the patient.
  2. In vivo (inside body). The CRISPR and Cas9 complex is delivered to the target area as a liquid nanoparticle. If needed in the circulation, for example to aid in the treatment of blood cancers, the nanoparticle will be delivered through IV administration.

More detail can be found on CRISPR Therapeutics website. 


 Is CRISPR currently used in therapy?

CRISPR is an extremely new therapy which is predominantly still in the recruitment stages for cancer clinical trials, taking place worldwide in the UK, USA and China, to name a few. CRISPR is currently heavily used to treat neurological problems, therefore is a promising scientific focus for the future. The National Institute of Health (NIH) is currently using CRISPR to tackle myeloma, sarcoma and melanoma. Blood borne cancers are a major focus of present, reprogramming the body’s immune cells to recognise and attack cancer cells at the first signs of growth. Immune cells contain a PD-1 receptor (the immune cells ‘off’ switch), which many tumours up-regulate to shut down our bodies natural immune response. The aim, to reprogram and disable the PD-1 receptor to give our immune system the fighting chance that cancer originally took away.


Off- target Mutations – debunked

A recent Nature article has been shown to shine light on potential secondary mutations associated with CRISPR, and has seen the stocks of companies such as CRISPR Therapeutics drop consequently. This unexpected news has caused anxiety in the field of biomedical research as this is obviously a dangerous and unwanted result of gene editing.

However, it can be argued that the paper does not provide enough evidence to support this claim at all. The variations and mutations reported in this article are significantly higher than other reports of CRISPR’s off-target mutations. Perhaps due to the following; the study used two sibling mice, with a distantly related mouse as a control. Could these unwanted mutations be due to predisposed variations, not caused by CRISPR? Surely the control should also be a sibling mouse in that case. Furthermore, this study uses an n of 2. That is certainly not a high enough sample size for such a damaging statement to be made regarding CRISPR.

It should also be noted that recent improvements have been made by genetically modifying the guide RNA to reduce any off-target mutations. Several groups have also developed web based tools to identify CRISPR target sites along with their potential off-target events.


My personal opinion shadows the views of the majority, that biomedical research has gone leaps and bounds with CRISPR and we hold huge hopes for this treatment of the future. Clinical trials are underway to treat cancer, with some expecting to be completed in 2018. Trials are also taking place for hereditary conditions such as muscular dystrophy with many scientists ‘moving their labs over to CRISPR’.


Information has been adapted from a pharmacology lecture by Dr. Shankar Varadarajan (Molecular and Clinical Cancer Medicine, University of Liverpool) in association with North West Cancer Research UK. Video / diagram taken from Cancer Research UK.