Unlimited potential for gene editing


Indian companies have wasted no time adopting new technologies, and CRISPR is no exception

Published in 2003, the first complete sequence of the human genome sparked a scientific revolution in our understanding of how differences in gene sequences have led to different functional effects within biological systems. We now had the basic sequence information for thousands of genes, but it was like having a complete dictionary of words with the associated definitions missing – understanding how genes interacted with each other and the impact. small differences in DNA sequence were missing.

To make the most of this wealth of new DNA information, tools for manipulating sequences in the context of living systems were needed. It wasn’t enough just to know that there were differences in DNA; knowledge was needed to understand how sequence differences affect gene function.

The advent of DNA manipulation

Interestingly, it was also in 2003 that the first tool to manipulate DNA in vivo was introduced. Based on a class of proteins called zinc finger proteins, this first-generation tool allowed scientists to introduce a cut in the DNA of a living organism at a predefined site and then manipulate certain changes there. Zinc finger nucleases were revolutionary in what they could accomplish, but had the downside that every single targeting event required quite a large design effort, which was neither easy nor inexpensive.

Further development in this space came in the form of effector transcription activator-type nucleases (TALENs) several years later. Although much simpler in design to target different sequences, the construction of each tool itself was cumbersome and the end product extremely large and difficult to manipulate in cells.

Enter CRISPR

In 2012, the world discovered a third generation gene editing tool courtesy of Dr Emmanuelle Charpentier and Dr Jennifer Doudna. They received a Nobel Prize in 2020 for their work on the discovery of the CRISPR / Cas9 gene editing system.

Scientists around the world now have an accessible platform that can be applied to virtually any species, from bacteria to plants, to the most complex species, including humans. CRISPR / Cas9 regularly makes headlines around the world. In recent months, the highlights have been human treatments for Alzheimer’s disease (1), sickle cell disease (2) and HIV (3). There have been countless stories of drug discovery, improvements in agricultural science, and innovation in environmental impact. Precision gene editing has a long reach and will impact many facets of life.

CRISPR / Cas9 in India

In India, at the government level, advances in biotechnology have been the focus of concern for some time. As early as 1982, biotechnology was on the radar of the then Prime Minister, the late Rajiv Gandhi. Following extensive deliberation, the Indian government in 1986 established a separate Department for Biotechnology within the Ministry of Science and Technology. In keeping with this trend, Indian companies have wasted no time adopting new technologies, and CRISPR is no exception.

Most notably, India is leading the way when it comes to COVID-19 testing. The revolutionary “Feluda” test was developed by Tata Medical and Diagnostics Ltd. -IGIB) based in New Delhi. It was the world’s first rapid paper-based test for the detection of COVID-19 and enabled rapid and affordable mass testing. The Feluda test has since been adapted to quickly detect mutated variants, as the test provides results in 45 minutes and only requires a basic PCR machine – more complex machines such as those running RT-PCR take longer. to run and return the results.

A second truly inspiring use of CRISPR comes from different, but no less globally important, areas of agricultural research. The Indian Council of Agricultural Research (ICAR) and the Department of Biotechnology (DBT) are working together to realize the potential of CRISPR gene editing technology.

Indian scientists are also enabling a change that will make the world a better place – researchers in India and the United States have discovered 29 genes in mosquitoes that cause malaria that make mosquitoes resistant to insecticides. About 2% of malaria deaths worldwide occur in India, and up to 1.3 billion Indians are considered “at high risk” of becoming infected with malaria. Discovering a way to neutralize and potentially limit the threat of malaria would have an incredible impact on healthcare around the world.

Researchers from the Institute of Bioinformatics and Applied Biotechnology in Bengaluru, the University of California and the Tata Institute for Genetics and Society (TIGS) collaborated to produce a new reference genome for a sample of the malaria vector mosquito from Turkey. Knowing the entire genome, researchers are applying CRISPR to modify “insecticide-resistant” genes in mosquitoes in an attempt to understand how they might one day eliminate these forms of resistance.

There are currently many projects that can significantly change daily life in India. From health and the environment to agriculture and bioenergy, using gene editing is part of planning to tackle previously seemingly insurmountable challenges.

What’s next for India: biosimilars?

Experts believe that biosimilars are essential for the future of affordable health care. This is especially true for a country like India, where they lead to more competition and innovation in the market. Biosimilars lower prices and allow better access to medicines for patients. India has firmly established itself as a world leader in the production of similar organic products, and due to its population of 1.39 billion, India is also a huge market for these products.

Although the potential is high and the expectations huge for India, the challenges are enormous in order to maintain the global leadership in this area. To achieve this, Indian biopharmaceutical companies must adopt CRISPR.

Although many Indian companies have deciphered the complex know-how of producing biosimilars in microbial and mammalian platforms, there is a need to focus more on gene editing technology. Even companies that have a head start in domestic markets are still struggling with manufacturing performance and production efficiency issues, and are exploring organic and inorganic ways to improve.

Given the criticality of time to market in the biosimilars sector, it is important to support timely access to technologies that will allow companies to gain entry into the competitive market or maintain a market position. leader. Companies in this field that do not use CRISPR / Cas9 must adopt this new technology or risk being left behind.

What’s next for CRISPR around the world?

Because of its ease of use and low cost, CRISPR has already opened up the use of genome editing to disciplines that had not even considered it before. Outside of human disease applications, gene editing is used to create greener chemistries and enable the use of microbes to create industrial products that, before CRISPR, required precious natural resources. To further support a sustainable future, gene editing will be used to modify crops to better withstand changing global climatic conditions and increase food production. Gene editing is likely to become a major player in the treatment of genetic diseases. Perhaps in the same way that software has evolved to manipulate computer and robotic hardware, gene editing will also serve as a “coding tool” for exploring and exploiting biological material in living systems. The potential is limitless.

Eric Rhodes, Managing Director, ERS Genomics, Ireland


Comments are closed.