CRISPR: Editing the world, one genome at a time

Where does CRISPR come from? How does CRISPR work? Find the answers in this review of: A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. Science. 2012 Aug 17;337(6096):816-21. doi: 10.1126/science.1225829.

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The ability to edit the genome is finally here, thanks to the 2020 Chemistry Nobel Prize winners Jennifer Doudna and Emmanuelle Charpentier. Their work on developing the clustered regularly interspaced short palindromic repeats (CRISPR) technique has revolutionized the field of gene editing. With this new technology the ability to cut and modify genomes opens doors to creating disease resistant crops, livestock with enhanced genetic traits and the ability to cure diseases. The CRISPR concept was originally developed from analysing the immune system of bacteria and archaea. It was discovered that they store viral DNA from past infections in their genome at the CRISPR locus. When another infection occurs, the bacteria can recognise the invading DNA and initiates the CRISPR-Cas9 complex to unwind and cleave the viral DNA, disabling it. The complex is made up of three components; the template RNA strand, an endonuclease called CRISPR-associated (Cas9) and another RNA strand called trans-activating crRNA (tracrRNA). To enable genes to be modified, the template RNA strand can be altered to target a specific gene sequence. When it is found, the complex forms a precise break in the DNA. Scientist can allow the DNA to repair itself and examine genetic mutations that arise, or they can insert a gene sequence to match the cut DNA sequence and allow recombination to embed their desired DNA into the genome. Both techniques allow scientists to analyse the gene expressions that occurs after gene editing has taken place.

There are several trials taking place around the world using the CRISPR method. In December 2020, two people were cured of their lifelong genetic disease, sickle cell anaemia. The evidence of their gene modification success can be seen in their blood and bone marrow DNA. Their corrected gene expression means they no longer require blood transfusions and are free from vaso-occlusive episodes. CRISPR has also been used to develop a new COVID-19 test that generates faster results than current methods. The aim of the test is to assist in controlling the spread of COVID-19 and hopefully lead to a life free from extended lockdowns. With more exciting advances in our knowledge of the CRISPR Cas9 complex, the global burden of disease could be significantly lowered. With many other trials underway showing positive results on crops and livestock editing, soon CRISPR-Cas9 will help scientists everywhere, edit the future of the world… one genome at a time.

Creator: R. Menzie

References:
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