Putting the gene editing tool to use

Researchers in India can use CRISPR-Cas9 only for academic purposes

When you edit a letter or a document, you make specific changes in the words and phrases to make the meaning clearer. Gene editing involves changing the sequence of DNA using specific enzymes which can cut DNA at a precise location, thus permitting the removal, addition, or replacement of genetic information within a gene. The process is akin to correcting a misspelt word in a sentence or replacing it with a more appropriate word. In organisms, this modification directly alters the genetic instructions encoded in the DNA.

In earlier days, if we wanted to modify the message in the DNA to a desired function, it involved two enzymes — one to cut the DNA at a specific site, and another to help insert the desired genetic change. While such twin-enzyme methods worked, they were laborious.

The discovery

This was when Drs Jennifer Doudna of University of California, Berkeley, U.S. and Emmanuelle Charpentier of Humboldt University, Germany came out with a double action gene modification method, called CRISRP-Cas9. This is a mechanism that can edit the genomes of humans, pathogens, and plants. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and Cas9 (which stands for CRISPR- associated Protein 9) cuts DNA strands at a specific location, creating a gap that can be filled with new DNA. Doudna and Charpentier shared the Nobel Prize in 2012.

However, Prof. Feng Zang who was then at a Southern California University, published a paper wherein he showed genome engineering using the CRISPR-Cas9 system. But he was not included as the third scientist by the Nobel Committee. He then went ahead, obtained a patent and moved to Boston, where he works and this patent is owned today by the MIT-Harvard University combine, called Broad Institute, which uses the CRISPR-Cas9 system for a variety of applications such as the mouse model for cancer, identifying genes that make cancer drugs ineffective, and modification of immune cells, plus training people in the technology. 

Gene editing in plants

While CRISPR-Cas9 patented technology has been used for the above-mentioned diagnostic and genetic uses, agricultural scientists and botanical researchers have been using this method to genome engineer plants. The group of Dr Holger Puchta of the Karlsruhe Botanical Institute, Germany has published several papers, notably how to use Cas9, Cas 12 and Cas13, for targeting plant genomes. Most recently, CRISPR-Cas9 based ‘knock-out’ of two genes in tomato plants increased their sweetness with no loss in weight. Similar studies on other plants and fruits will surely follow.

However, a recent report by Dr Anurag Chaurasia, titled “How CRISPR patent issues block Indian farmers from accessing biotech benefits”, points out that the IPO has granted a local patent to ERS Genomics of Dublin, which allows Indian researchers to use CRISPR-Cas9 only for academic purposes but not commercialise any scientific breakthroughs. Our rural farmers are thus still left ‘classical’.

Visually handicapped

For people afflicted with eye disorders, scientists and clinicians at LV Prasad Eye Institute, Hyderabad, in collaboration with a group in IGIB, have used one of these high precision methods to correct inherited mutations in patient-specific stem cells (Nature Communications, June 2024). These mutation-corrected stem cells could then make retinal cells, which showed restored expression of the missing protein. This has opened the possibility of developing autologous cell therapies for certain inherited eye disorders. A similar approach can be adapted for other diseases affecting other tissues and cell types of the body.