CRISPR & Gene Editing

About CRISPR

• Unusual but repeated DNA structures that scientists had been observing were given a name — Clustered regularly interspaced short palindromic repeats or CRISPR.
• In 2012, scientists discovered that CRISPR is a key part of the “immune system”. For instance, when a virus enters a bacterium, it fights back by cutting up the virus’s DNA. This kills the virus but the bacterium store some of the DNA.
• The next time there is an invasion, the bacterium produce an enzyme called Cas9 which matches the stored fingerprints with that of the invader’s. If it matches, Cas9 can snip the invading DNA.

Components of CRISPR Cas 9 Gene Editing Tool

• The CRISPR-Cas9 gene editing tool thus has two components — a short RNA sequence that can bind to a specific target of the DNA and the Cas9 enzyme which acts like a molecular scissor to cut the DNA.

Gene Editing using CRISPR

• To edit a gene of interest, the short RNA sequence that perfectly matches with the DNA sequence that has to be edited is introduced.
• Once it binds to the DNA, the Cas9 enzyme cuts the DNA at the targeted location where the RNA sequence is bound.
• Once the DNA is cut, the natural DNA repair mechanism is utilised to add or remove genetic material or make changes to the DNA.
• Dr. He used the CRISPR–Cas9 gene editing technique in the twin girls to disable a gene called CCR5, which encodes a protein that allows HIV to enter and infect cells

Issues with gene tool?

• There is a general consensus in the scientific and ethics communities that the CRISPR–Cas9 gene-editing technique should not be used clinically in embryos
• There is also consensus that gene editing can be potentially used only to prevent serious genetic disorders that have no alternative treatment. While HIV cannot be cured, medicines can keep the virus under check.
• Importantly, human clinical trials have not been carried out anywhere in the world to test whether disabling the gene completely prevents HIV infection and what the side-effects of doing so would be. In the absence of any clinical trial data as well as consensus to use this tool to prevent HIV infection, performing it on babies as a form of medical intervention is unethical.
• Dr. He used the CRISPR–Cas9 gene editing technique in the twin girls to disable a gene called CCR5, which encodes a protein that allows HIV to enter and infect cells.

Can disabling the CCR5 gene prevent HIV?

• While it is generally believed that babies without a functional CCR5 gene will become resistant to HIV infection, certain other strains of HIV use another protein (CXCR4) to infect cells. Hence, even people who are born with two copies of the non-functional CCR5 gene are not completely protected or resistant against HIV infection.
• There is also the possibility that the gene editing tool could have caused unintended mutations in other parts of the genome, which may lead to unpredictable health consequences.
• Most importantly, medicines and delivery through caesarean section and avoiding breast feeding can prevent vertical viral transmission from mother to foetus. While women with HIV have greater chances of passing the virus to the foetus, in this case, the mother was HIV-free; the father was HIV positive.

Protective role of CCR5 Gene?

• The CCR5 gene’s protective role against the West Nile virus is well established, the CCR5 gene can also helps to protect the lungs, the liver and the brain during certain serious infections and chronic diseases.
• The gene is known to prompt the immune system to fight the influenza virus in the lungs. Without this gene the defence system would fail. In the case of people with multiple sclerosis, absence of this gene makes them twice as likely to die early.

Recent Updates on CRISPR

Context: The Tata Group has unveiled India’s first CRISPR test.

About CRISPR test

• The Tata CRISPR test has been developed by CSIR-IGIB ‘Feluda’ (Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology) and ICMR.
• It has received regulatory approvals from the Drug Controller General of India (DCGI) for commercial roll-out in accordance with the Indian Council of Medical Research (ICMR) guidelines.
• The test has met high benchmarks, with 96% sensitivity and 98% specificity for detecting the novel coronavirus. 
• It uses indigenously developed CRISPR technology for the detection of the genomic sequence of the SARS-CoV-2 virus.
• The Tata CRISPR test is the world’s first diagnostic test to deploy a specially adapted Cas9 protein to successfully detect the virus causing COVID-19. 
• The Tata CRISPR test achieves the accuracy levels of the traditional RT-PCR (real-time polymerase chain reaction) tests, with quicker turnaround time, less expensive equipment, and better ease of use.

Benefits 

• It is a high-quality test that will help India ramp up COVID-19 testing quickly and economically, with a ‘Made in India’ product that is safe, reliable, affordable, and accessible.
• It has high sensitivity and specificity for detecting the novel coronavirus. 
• It achieves the accuracy levels of the traditional RT-PCR (real-time polymerase chain reaction) tests, with quicker turnaround time, less expensive equipment, and better ease of use.