Q. Explain the CRISPR-Cas9 gene-editing technology. Discuss, in Indian context, the benefits and challenges associated with genomics revolution. (250 words)

Model Answer :

Approach:

• Why in news?
• Gene-editing and CRISPR-Cas9
• Benefits associated with genomics revolution
• Challenges associated with genomics revolution
• Conclusion

Why in news?

• Recently, three studies related to CRISPR-Cas9 gene-editing were published in the scientific journal, Nature Medicine.
• US scientists have successfully edited the DNA of human embryos to erase a heritable heart condition that is known for causing sudden death.
• In May 2017, it was shown that in mice it is possible to shut down HIV-1 replication and even eliminate the virus from infected cells.
• Researchers from the Oregon Health and Science University in California, China and South Korea repaired a mutation in human embryos by using a gene-editing tool called CRISPR-Cas9.
• Clinical trials are under way in China and in the US to use this tool for treating cancer.
• In agriculture, a new breed of crops that are gene-edited will become commercially available in a few years.

Gene-editing and CRISPR-Cas9

Gene editing or genome editing is a way of making specific changes to the DNA of a cell or organism. An enzyme cuts the DNA at a specific sequence, and when this is repaired by the cell a change or ‘edit’ is made to the sequence.

CRISPR-CAS9 is a new gene-editing technology that promises to revolutionize genetic manipulations and made gene editing simpler, faster and easily accessible to most laboratories.

• CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)are sections of DNA and are sections of genetic code containing short repetitions of base sequences followed by spacer DNA segments.
• CAS-9 (CRISPR-associated protein 9) is the enzyme which acts as a “molecular scissors” and helps in cutting the DNA sequence.
• CRISPR scans the genome looking for the right location and then uses the Cas9 protein as molecular scissors to snip through the DNA.

In simple terms, a DNA sequence is cut at a particular spot and then with help of a guide RNA (gRNA) that place is re-made with desired base pairing. This way genes can be altered. It allows scientists to selectively edit genome parts and replace them with new DNA stretches.

Benefits associated with genomics revolution

• It can help in linking specific illnesses to features in the genome. In India, blood-related disorders such as haemophilia, sickle cell anaemia, and Beta-Thalassemia, and other disorders such as Duchenne Muscular Dystrophy are promising candidates for gene editing.
• The genetic distinctiveness of different Indian groups is in part the result of endogamy. Endogamy is very likely to be medically significant as there are likely to be many recessive diseases stemming from single genes specific to individual groups that can be identified. This knowledge could then also be quickly applied to the task of managing diseases in these groups as well as be used for genetic counselling that could reduce their incidence in future generations. For example - The founder group of Ashkenazi Jews have almost eliminated Tay-Sachs disease from their population by such means.
• With large samples the technique of “genome-wide association studies” that compare genomes of cases and controls could be used to identify genetic risk factors related to common diseases (such as heart disease that stem from many genes) that affect the health of many more individuals.
• Surveys of Indian genetic diversity will help to uncover the basic biological function of genes and their interactions, which are not yet fully understood. This knowledge will be useful to humanity worldwide and also offer India a chance to claim a piece of the global medical and scientific frontier.
• India’s agricultural researchers can apply this technology to breed newer varieties of crops endowed with better traits like resisting pests and improving their nutritional values. Such varieties of plants will reduce use of chemical fertilizers that harm human health and environment.
• Besides crop, Genome technology can enable livestock improvement that can potentially end hunger and improve the standard of living not only in India but across the world.
• It makes it easier to do engineering and enhancement on plants and animals, for agriculture, and also on humans, for medicine and enhancement, then finally, on the environment For example - This technology can be used to produce mosquitoes that cannot pass along malaria, or to reverse greenhouse gas increases and ocean acidification. 
• As a large part of the enterprise would be the application of information technology or “bio-informatics”, the prospects of establishing viable commercial enterprises with synergies to existing IT champions are also promising.

Challenges associated with genomics revolution

• In India, only a small number of hospitals are using genetic information to help patients, and there is at least one private sequencing company in India. But all of this activity is on a much smaller scale than needed and is currently not generating the manpower required to equip the next generation of medical and research activities in the area.
• As India is much more genetically diverse — with something like 5,000 ethno-linguistic and religious groups (castes and others), all of which probably have some degree of genetic distinctiveness — it needs a larger survey to collect and store genetic information of its citizens in a data base, Also, this data should be utilized for treatment and research purposes.
• Besides the collection of information about the genetics of its population India needs to train manpower capable of interpreting it.
• Both genetic data and biological samples are easily transported across borders and if Indian regulation is shortsighted, it will simply cause Indian genomics to move abroad to places such as Singapore. The GenomeAsia 100K Initiative based in Singapore plans to sequence 100,000 Asian genomes, including some from South Asia. While this is eminently worthwhile as it will provide a broader pan-Asian set of data, it would be important to make similar investments at a national scale quickly to avoid the situation that this is one of the only enterprises to which Indians can turn to.
• Two studies published recently in the scientific journal, Nature Medicine, have highlighted that CRISPR-Cas9-edited cells might trigger cancer.
• Another study published recently in the scientific journal shows that both the mouse and the human gene edited cells (using CRISPR-Cas9 system) suffered from large DNA deletions far from the intended editing sites. This raised question mark over its proposed clinical usage.

Conclusion

All in all, the time is ripe for India to begin its own genomics revolution. The technical understanding and will needed to launch this is present in India’s scientific leadership, in medicine and in industry. What is needed is a vision and leadership at the national level to leverage this and seize the day.