These days Debojyoti Chakarborty, 37, a genetic engineer with the Institute of Genetics and Integrated Biology (IGIB), Delhi, and his colleagues are busy with pre-clinical studies of a genetic therapy that has the potential to cure a person suffering from sickle cell anaemia (SCD), a red blood cell disorder that can lead to stroke, serious infections, pain, and chronic chest obstruction.
SCD is a genetic disorder caused by mutation in a gene called Haemoglobin-S. “Genes exist in a pair. We get one from the father and the other from the mother. SCD occurs when these genes are defective. The disorder affects thousands of people in India,” says Chakarborty.
Genes are fragments of DNA (deoxyribonucleic acid), and DNA is a molecule which carries the genetic instructions, or hereditary materials, that define your characteristics. Your DNA (or RNA in some organisms), including your genes, and other elements that control the activities of these genes, constitute your genome.
Genetic engineering, which is the editing of human DNA, along with an evolving field of science called synthetic biology, which allows scientists to design and construct biological parts, biological systems, and even organisms, are all set to revolutionise healthcare in the coming years.
It has the potential to eradicate many deadly diseases and address emerging health issues, help devise fast and efficient diagnostic tools, and even deal with deadly microbial resistance. In fact, researchers across the world, including India, are using synthetic biology to find newer diagnostic methods, drugs, therapies, and treatments. Biologists say this is the future of medicine as it will reduce costs, and increase efficiency and reliability in healthcare.
“If the entire genome is like a piece of writing, SCD occurs due to a mistake in one alphabet. We are developing a technique to correct this faulty alphabet. We do it with the help of a molecular scissor called CRISPR-Cas9, which not only cuts but also has an ability to repair defective genes. If we can correct the defect in small children suffering from SCD, they can be cured of the disease and have a better quality of life,” says Dr Souvik Maity, Director, IGIB, Delhi.
Research on this is being funded by the Ministry of Tribal Affairs and the Department of Science and Technology (DST), and is being conducted at five institutes, including IGIB and AIIMS, Delhi.
“From genetically modifying an adenovirus to overcoming liver cancer to treating severe spinal cord injuries, synthetic biology is being used by researchers across the world,” says Ashwin Jainarayanan, a Ph.D. scholar at Oxford University.
Jainarayanan, 30, is working in the field of synthetic immunology using synthetic DNA to find a cure for pancreatic cancer. “Vesicles are like nano vessels secreted by cells and generally carry waste material. Vesicles secreted by cancer cells, however, also help them find a favourable environment to metastasise (spread). I am working on a mechanism to re-engineer these vesicles and load them with synthetic toxins to increase their cytotoxicity, to target and kill the cancer cells,” said Jainarayanan, who is at the final stage of his research. His work, if successful, can be used to develop an effective treatment for pancreatic cancer, which has a high mortality.
Jainarayanan believes that synthetic DNA offers enormous possibilities. “You can actually collect DNA fragments from different organisms, clone them into a vector, and introduce them in an organism for the desired function. It can help us develop treatment for many diseases in the future,” he said.
In fact, synthetic biology is a huge area of interest for biologists across the world and is attracting millions of dollars of investment. Synthetic DNA, explains Maity, has two applications — the first is therapeutic, and the second is that it allows us to understand new biology.
“There are some non-coding RNA molecules, called micro RNA, involved in the regulation of gene expression. Some of these micro RNA can cause serious diseases. To suppress these disease-causing micro RNAs, we can use synthetic DNA called antagomir,” said Maity. “Though in India we are focussing on research, other countries are at advanced stages of clinical trials. Soon, synthetic biology will offer treatments for diabetes and cancer,” Maity added.
Dr Samir K Brahmachari, a noted genetic scientist, said that in 2010, India wanted to set up an institute dedicated to synthetic biology. “ But I was not sure if we could find the right candidates for the institute. So, to find a deserving team, we offered grants to researchers to participate in the International Genetically Engineered Machines (iGEM), one of the world’s biggest competitions organised by Massachusetts Institute of Technology (MIT), where geneticists and biologists from across the world come to participate,” added Brahmachari.
“We were surprised by the performance of the Indian teams, who won many prizes for their extraordinary work. And our journey began,” explained Brahmachari, who was then Director General, Council of Scientific & Industrial Research (CSIR), a premier national R&D organisation. “CRISPR-Cas changed the game. Now you can design a gene, modify it, and delete it,” he added.
“Not just medical science, synthetic biology may hold solutions to many stubborn agricultural and environmental problems too. It is the future,” said Maity.
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