CRISPR will open doors for therapeutics and gene-editing
Bacteria and archaea possess their own adaptive immunity known as CRISPR-Cas system to protect against viruses. Scientists have proposed that this system can be engineered to become the fastest, cheapest and easiest gene-editing tool. The principle behind this is that bacteria contain a library of short snippets of RNA within their genome that match that of invading viruses; this is known as the CRISPR region because it consists of Clustered Regularly Interspaced Short Palindromic Repeats.
Every time a virus injects its DNA into the bacterium, the cell makes an RNA copy of this to produce crRNA (CRISPR-RNA) that will act as a template. The purpose of this is to guide a CRISPR-associated protein (Cas) to the matching viral DNA sequence and breaks it down following recognition. As a result, the bacteria is protected from the virus because the viral DNA cannot be replicated and therefore, infection cannot occur. This system is adaptive because every time a virus with a new genome is encountered, Cas protein will degrade this so that the bacterium will contain shorter RNA version in its CRISPR region like a library. The bacteria is now resistant and will generate a faster response in the future.
Scientists have high hopes to replicate this system in the laboratory, this will allow a level of control in experiments and aim to gain a better understanding of the significance of certain genes. The specificity and high reproducibility of CRISPR-Cas9 deems it favourable to other methods, like in RNA interference where the gene of interest might not be completely turned off in order to study the impacts of its absence. By overcoming these issues, this could open doors and accelerate the drug discovery process and even correct genes responsible for diseases.
In 2016, You, L et al in China were the first to attempt to treat a patient, suffering from lung cancer, utilising this mode of gene-editing by targeting the genes encoding abnormal PD-1. Normally this protein acts as an immune checkpoint to promote or demote apoptosis (controlled cell death), but the dysfunctional form struggled to regulate this and this led to the progression of the aggressive cancer. The use of CRISPR-Cas9 rendered PD-1 disabled so that other immune cells could target the tumour cells and improved the condition of the patient. This trial is a key milestone for gene-editing but it should be noted that this is still not extensively used as it cannot be guaranteed that all human immune systems will react the same, as well as the ethical concerns associated with genome editing.
Much more research is required to perfect the method such as fine-tuning delivery to infect only the cells that need to be edited; one approach to tackle this is by trying different Cas proteins that make different types of cuts in the genetic material depending on what change you want to make. The use of Cas13 has the potential to treat COVID-19 because this protein targets RNA and SARS-CoV-2 is known to be an RNA virus rather than DNA. This differs from the traditional approach of vaccines that requires the activation of the adaptive immune system, which takes longer than genetically reprogramming cells. However, again further studies need to be taken to test the safety and ensure that this will not give rise to unfavourable mutations.
