CRISPR: A revolution in medical science
- Daily Dose of Medicine
- May 12, 2021
- 3 min read
What is CRISPR?
Clustered Regularly Interspaced Short Palindromic Repeats, more commonly known as ‘CRISPR’(1), is a powerful tool for editing genomes and allows researchers to easily modify gene function (2). This technology was adapted from our natural defense mechanism of bacteria and archaea (2).These organisms use CRISPR-derived RNA and various Cas proteins, including Cas9, to foil attacks by viruses (2).
Where did the idea of CRISPR come from? CRISPRs were first discovered in archaea (and later in bacteria) by Francisco Mojica, a scientist at the University of Alicante in Spain. He proposed that CRISPRs serve as part of the bacterial immune system, defending against invading viruses(1).
There are 3 steps involved with CRISPR; adaptation, production and targeting. Adaptation is where the virus invades the bacterial cell and DNA from the invading virus is processed into short segments, inserted into the CRISPR sequence as new spacers (3). Production of CRISPR RNA happens when CRISPR repeats and spacers in the bacterial DNA undergo transcription,( the process of copying DNA into RNA), this results in RNA being a single-celled molecule, unlike the double-helix structure of DNA. This RNA chain is cut into CRISPR RNAs (3). Targeting is where CRISPR RNAs guide bacterial molecular machinery to destroy the viral material. The CRISPR RNA sequences are then copied from the viral DNA sequences gained in adaptation (3).
Once a specific DNA region is matched by the gRNA (guide RNA, a piece of RNA that functions as a guide for RNA targeting molecules) carrying Cas9 (a protein that plays an important role in the defense of bacteria against viruses), the target DNA is cleaved with a double stranded break. Cas9 RNP (a way to deliver CRISPR components) complexes can be introduced into cells directly and act immediately after they enter the cell without transcription and translation. By matching the gRNA sequence with different functional domains, the CRISPR/Cas9 system and its variants have been used for a broad range of gene editing applications (4).
Applications of CRISPR
CRISPR has been extensively used in research since its first application in genome editing in 2012. There is a reasonable justification for this - CRISPR is considerably more effective, safer and quicker than genome editing techniques that came before it (i.e., TALENs & ZFNs). CRISPR has impacted many industries like agriculture and energy; the genome editing technique has certainly had a great influence in medical sciences, this can be demonstrated using a wide range of examples.
In 2018, a new type of cancer immunotherapy was investigated in 3 cancer patients as part of a phase 1 clinical trial. The therapy involves collecting T lymphocytes (immune cells that kill cancerous cells) from the patients’ blood and then editing their genome using CRISPR to insert a gene that codes for a specific cell surface membrane receptor. This enables the lymphocytes to bind to specific antigens (NY-ESO-1) that are present on some cancer cells (leading to eradication of cancer cells). Fortunately, the trial concluded that the therapy did have a small effect on the patients’ cancers – the growth of tumours of 2 patients stopped temporarily, though the therapy did not work for the other patient. (5)
Sickle cell disease is disease that results in crescent moon shaped red blood cells. The main symptoms of the disease include anaemia, stroke and swelling of extremities. Treatments that exist today for the genetic condition are only able to reduce the severity of the symptoms associated with it. Apart from bone marrow transplants which is uncommon due to the low presence of available donors, there are no effective cures for sickle cell disease. Remarkably, the CTX001 clinical trials have shown promising results in the treatment of a patient using a new gene therapy. The therapy involves collecting blood cells from the patent and then editing a specific gene using CRISPR so that the cells produce a type of haemoglobin that has a higher affinity for oxygen than adult haemoglobin – fetal haemoglobin. The patient the gene therapy was trialled on experienced a substantial improvement in their sickle cell symptoms. (6)
Written by Ellie Green and Nelson Neekilas
Bibliography
(6) https://www.synthego.com/blog/crispr-cure-diseases#curing-blood-diseases-using-crispr-technology
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