Introduction
Advancements in science and technology have made gene-editing and the creation of genetically modified organisms (“GMOs”) a reality. It is now possible to alter and modify the genetic makeup of living organisms, leading to breakthroughs in agriculture and medicine. Such technologies and practices are being widely adopted across the world, including India, where gene editing is being explored primarily in agriculture to develop climate-resistant crops such as BT Cotton, BT Brinjal, GM-Mustard, etc. The global genome editing market, valued at $3.41 billion in 2024, is projected to reach $4.25 billion in 2025 and $13.36 billion by 2035, representing a CAGR of 12.1% during the forecast period[1].
Gene editing involves altering an organism’s existing genes, whereas GMOs typically involve inserting foreign DNA into the cells of an organism. In this context, various gene-editing technologies have emerged, such as Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and CRISPR/Cas9 (“CRISPR”), each offering different levels of precision and efficiency. Out of these technologies, CRISPR seems to have gained prominence due to its simplicity, cost-effectiveness, and accuracy. In India, for instance, scientists have utilised CRISPR technology in plant genome editing especially, like development of mustard seeds with reduced glucosinolate content[2], drought and salt-tolerant rice, vitamin A-fortified bananas, etc.[3]
CRISPR’s above-mentioned application indicates growth in scientific research and innovation in plant genome editing. Given the delicate sphere of genetic engineering, it is pertinent to understand the Indian regulatory regime that should ensure and balance safety, ethical concerns and scientific development when it comes to genome editing. In this context, this blogpost series seeks to delve into the basic science behind CRISPR and the regulatory approvals, from testing to commercialisation, of CRISPR modified crops in India.
Brief Overview of CRISPR
All living organisms are made up of DNA, which is the genetic material arranged in a particular sequence within their cells. This genetic material basically acts as the instruction manual, determining the characters and functioning of an organism. Gene editing allows for altering the DNA sequence such that a particular part of the sequence is changed by removing or adding a new sequence of genetic material. CRISPR is one such gene editing technology that is used to alter genetic sequence in living organisms, especially plants.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), based on bacteria’s natural self-protecting mechanism, is a powerful gene-editing tool that works like a molecular scissor to alter DNA, in a targeted manner, by cutting it at specific sites to either disable a gene, correct mutations, or insert new genetic material, CRISPR can cut, repair and add genetic material.[4]
The CRISPR technology, often referred to as the CRISPR/ Cas-9 technology, basically involves two main components — a protein called the Cas-9, and a Guide RNA (gRNA). The Cas-9 protein acts as the ‘scissor’ that cuts the DNA, and the gRNA, as the name suggests, guides this Cas-9 protein towards the target area. Therefore, the main steps in the functioning of CRISPR/ Cas-9 are:
(Illustration Source: https://www.gao.gov/products/gao-20-478sp)
- Identification of the target area: Once the issue to be treated in the genetic material is identified, the gRNA is designed in such a manner that it reflects the specific DNA sequence that has to be altered, and finds the exact location where such a change is required in the DNA.
- DNA slicing: Once the gRNA identifies the target genetic sequence, it brings forth the scissors, i.e. the Cas-9 protein, which then makes a cut at the targeted spot.
- Repair of the DNA: It is at this stage, post cutting of the DNA, that either a new gene is inserted at the cut spot, or a faulty gene is prevented from working since the cut can break the DNA sequence and stop it from working any further.
As mentioned above, CRISPR works by identifying a particular spot in the genetic material that requires alteration. This alteration is done using ‘site directed nucleases’ (“SDNs”), which allows for breaking of the genetic material where alteration needs be undertaken. Basis the nature of breaks made by these SDNs and the kind of alteration done, CRISPR may be used for the following instances of gene editing:
- SDN-1: A break is created in the genetic material of the plant, but without adding a foreign DNA. Once the DNA is repaired, it results in deletion of the targeted genetic sequence, which could lead to gene silencing or a change in the gene activity.
- SDN-2: A break is created in the genetic material of the plant. While the cell repairs this break, a small genetic template, which is complementary to the sequence of the target area, is provided. It is then replicated in the genetic material of the plant, leading to modification of the targeted gene. No foreign genetic material is, however, provided in this technique.
- SDN-3: A break is created in the genetic material of the plant. While the cell repairs this break, a foreign genetic material is provided and replicated in the genetic material of the plant, leading to the introduction of new genetic material in the cell.
Ethical Considerations
Genetic engineering, specifically CRISPR, is gaining much global popularity and India is no exception. In India, CRISPR is being employed in agricultural advancements to develop disease-resilient crops and enhance crop yield. It can aid in the development of disease-resilient livestock, improving the quality and quantity of livestock products.[5] Having stated CRISPR’s potential benefits, it must be noted that this technology is also riddled with a range of ethical, social, and safety concerns that necessitate regulatory oversight. Such genetic alterations can lead to unintended mutations, with potentially harmful consequences. Further, issues of lack of oversight during research, testing, etc., could lead to lack of adherence to any ethical standards. Also, lack of transparency in research results is another issue that may need to be addressed. Another aspect to consider is how market forces may react if large-scale commercialisation of genetically engineered crops is permitted in India.
Part 2 of this blogpost series will focus on the regulatory regime surrounding genetic engineering, especially CRISPR.
*The authors were assisted by Sneha Smriti (Intern)
For further information, please contact:
Biplab Lenin, Partner, Cyril Amarchand Mangaldas
biplab.lenin@cyrilshroff.com
[1] https://www.rootsanalysis.com/reports/genome-editing-market.html#:~:text=The%20global%20genome%20editing%20market,12.1%25%20during%20the%20forecast%20period.
[2]https://indianexpress.com/article/explained/explained-economics/gene-edited-mustard-less-pungent-more-useful-8901549/
[3] https://www.nature.com/articles/d44151-024-00076-w#ref-CR1
[4] CRISPR gene-editing possible in temperature sensitive organisms, plants & crop varieties | Department Of Science & Technology (dst.gov.in)
[5] https://dst.gov.in/crispr-gene-editing-possible-temperature-sensitive-organisms-plants-crop-varieties
