Genetic Scissors: Nobel Prize in Chemistry, 2020 You may have heard the work gene. Genes contain DNA, a long molecule that contains a unique code. The DNA is usually wrapped around and compressed into chromsomes and are found in the nuclei of cells. The code in DNA is used by the organism to produce a specific protein molecule. All genes or DNA put together therefore code for all the proteins required to create the organism and are called its genome. Hence DNA and the genomes are the template which contain all the information to creat the organism, whether it is a virus, or human beings. (Some organisms have a different but similar molecule called RNA and not DNA). CRISPR/Cas9 in Bacteria Bacteria are small, but viruses are smaller still. And just like us, bacteria can also be infected by viruses. When viruses enter a bacterium, they infect it by leaving their DNA inside it. The bateria fight off the viruses. If they are successful, they do not just get rid of the attacking viruses. They do something more: they encode the virus into their own genes. A piece of the virus DNA gets inserted physically into the genome of the bacteria. This insertion occurs in what is called the CRISPR section of the genome. The virus DNA is easily identified by having repeated sequences of DNA between each viral DNA (see figure). How does this help? Actually, the bacteria makes two strands of RNA. Only one of them -- called the guide RNA -- contains the virus DNA. The two strands combine with a protein to make an enzyme (which can break the strands) called Cas9. Cas9 is also called a nuclease. Now suppose the same virus tries to infect the bacteria again. The portion of the guide RNA that contains the virus DNA matches up with the corresponding segment of the invading virus, and cuts it. This disables the virus, so that it cannot replicate and harm the bacteria. This was something that happened completely naturally. CRISPR-Cas9 as a gene editor Now scientists realised an amazing thing: you can change or edit the guide RNA and the Cas9 nuclease will then cut any segment of DNA that matches this edited portion! It is a molecular scissors! Not just this, but you can modify the Cas9 in such a way that it not only cuts out the unwanted segment, but it can also replace the cut-out part with another portion of DNA. Why is this such a powerful tool? Imagine that you have a faulty gene that results in some incurable disease. You can simply cut out this faulty part and replace it with some "normal" gene so that you automatically get cured of the disease! The potential of this technology is unlimited, but until now, CRISPR has only been used in modifying the DNA of eggs and living cells that were outside the body (and then re-introduced into the body). The tool has been used to change the DNA of animals and plants and micro-organisms as well. It has been an important way to breed plants that are resistant to certain disease-causing agents. But recently, in Mar 2020, Cas9 was directly injected into a patient. The results of this trial are hopeful but not completely known. BOX on What does CRISPR stand for? CRISPR stands for clustered regularly interspaced short palindromic repeats! If you try and understand each word, and put them together, you will understand what CRISPR does! Mostly CRISPR gene editing is done using the Cas9 gene. END OF BOX This year's Nobel prize in Chemistry was awared to two women scientists for the development of the CRISPR technique just 8 years ago, in 2012. They are Emmanuelle Charpentier and Jennifer A Doudna. Charpentier studied the bacteria called Streptococcus pyogenes whicg causes tonsillitis, a mild disease. But it can also cause a life-threatening condition called sepsis where the soft tissues of the body break down. She wanted to understand how the genes of this bacteria are regulated, to help control it. While Doudna was working on RNA, she discovered that there are a lot of small RNA molecules that help to regulate gene activity: just what Charpentier was looking for, working independently in another part of the world. Soon they met, and followed up on their suspicion that CRISPR-RNA was needed to identify the DNA of a virus, just as we saw earlier. They also thought that Cas9 is the scissors that can cut off the DNA molecule. But their experiments failed, again and again! They later realised that an additional RNA molecule was required to activate the mechanism. This was discovered by Charpentier and is called trans-activating CRISPR-RNA (tracr-RNA), which describes exactly what it does! When this was added, the Cas9 did indeed cut the DNA molecule. The two scientists did not stop there. They found out how to fuse the two tracr-RNA and CRISPR-RNA into a single molecule, which they called guide RNA (which we just learnt about). They then did the most amazing thing of all: they investigated to see whether this guide RNA can be controlled to cut the DNA at any location of their choice. The answer was yes, and the world had got a marvellous tool that is so widely used today. Possibility of misuse You can immediately realise that the tool is so simple, yet can be misused to create genetically modified human beings with specific traits. For example (not a reality today, but possible), apart from treating for serious disease, you can change the eye colour, hair colour, and create the "ideal" human being that society prefers! Also, you can modify plants in such a way that they take over and prevent local species from growing. So the regulation of such genetic engineering is very important. Sources: https://www.nobelprize.org https://www.sciencenewsforstudents.org/article/explainer-how-crispr-works https://crestcritique.com/701/stem/gene-editing-with-crispr/ https://en.wikipedia.org/wiki/CRISPR_gene_editing