New techniques in molecular biology usually take many years of development before they become common place. In comparison, a new genome-editing technique called CRISPR-Cas9 (short for ‘clustered regularly interspaced short palindromic repeats’) has taken over practically overnight.
First discovered in 1987 in a bacterium, CRISPR is part the adaptive immune system, fighting viruses and plasmids. In 2012, UC Berkley and the Broad Institute (a collaboration between MIT and Harvard University) both independently developed CRISPR-Cas9 as a programmable genome-editing technique. This triggered the scientific community to quickly recognize the potential of CRISPR, with the UC Berkley paper already having been cited over 3000 times.
CRISPR-Cas9 is used for genome-editing functions through a system of cutting enzymes, called Cas9, being directed by guide RNA, leading Cas9 to a specific spot on the invading DNA through complimentary pairing of the guide RNA to the invading DNA. Once the invading DNA is cut, the enzyme causes no further alterations to the DNA.
The brilliance is in the guide RNA, as it can be programmed by researchers. Through designing and synthesising just a short 20 base sequence of the guide RNA, it is possible to guide the cutting enzymes, Cas9 or Cpf1, to any sequence of DNA, in any organism, with high specificity.
CRISPR can be used to cut the genome and remove, add, or replace DNA sequences. Once DNA is cut, there are cellular mechanisms which try to fix it; these mechanisms are utilised with CRISPR to edit the genome. To remove a sequence, CRISPR can cut out the desired sequence and then simply stick the remaining exposed ends back together. To put in a new sequence, CRISPR is sent in with synthesised DNA containing the desired sequence to be added into the genome. CRISPR makes the cuts and then the desired sequence is copied into the gap, using the synthesised DNA as a template.
CRISPR is cheaper, quicker, and much easier to use when compared to its predecessors, which would cost thousands of pounds to carry out. CRISPR, however, can have a total cost of as little as £25 and requires just the design and synthesis of a RNA sequence 20 bases long, which, compared to the old methods, is like the difference between riding a bike and flying a fighter jet. Where older methods would take between months to years to carry out, CRISPR can be carried out in weeks or days, with much higher specificity than the older methods.
CRISPR, or a modified version of it, has the potential for treating all genetic diseases and age-related diseases. This includes even cancers, through editing immune cells to improve their cancer-spotting ability. These treatments are limited to the individual, but through modification of the reproductive cells or early embryos, it is possible to eradicate a genetic disease completely; this is called germ line therapy. The potential to edit reproductive cells and embryos on mass has sparked ethical, moral, and practical concerns, particularly in the context of designer babies and the inability to remove modification to the genome from a population.
Regardless, there is a race to get gene-edited cells into clinics across the world, particularly between China and the US. CRISPR is accelerating this race with clinical trials having already begun in China and the US towards the treatment of cancers and HIV. In 2016, a team at Temple University used CRISPR to successfully remove around 50 per cent of the HIV virus from an almost completely infected rat, demonstrating its incredible potential in treating HIV and other retroviruses in the future.
As the uncle of a genetically modified spider-human once said, with great power comes great responsibility, so to make the most of CRISPR we must tread carefully, a ban on the technique would be a huge loss to humanity. But whether we like it or not, the CRISPR revolution is here, and we should be immensely excited about it
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