CRISPR: beginning to deliver | Explained News,The Indian Express

Over the last two and a half years, as the coronavirus pandemic ravaged the world and exposed the vulnerabilities of humans to new diseases, scientists continued to push ahead with significant progress in utilising an exciting recent technology for permanent cures to some of the most intractable health disorders.

In the 10 years since it was developed, the genome-editing technology called CRISPR has begun to deliver on the near unlimited potential that scientists say it has to improve the quality of human life.

The technology enables a simple but remarkably efficient way to ‘edit’ the genetic codes of living organisms, thus opening up the possibility of ‘correcting’ genetic information to cure diseases, prevent physical deformities, or to even produce cosmetic enhancements.

Over the last three years especially, several therapeutic interventions using CRISPR for diseases like thalassaemia or sickle cell anaemia have gone into clinical trials, mainly in the United States, and the initial results have been flawless.

Last year, the Indian government approved a five-year project to develop this technology to cure sickle cell anaemia that mainly afflicts the tribal populations of the country.

And this is just the beginning. Hundreds of research groups and companies around the world are working to develop a range of specific solutions using CRISPR. The developers of the technology, Jennifer Doudna and Emmanuelle Charpentier, won the Nobel Prize for Chemistry in 2020, one of the fastest recognitions accorded by the Nobel committee following after a breakthrough.

The CRISPR technology

CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats, which is a reference to the clustered and repetitive sequences of DNA found in bacteria, whose natural mechanism to fight some viral diseases is replicated in this gene-editing tool.

Editing, or modification, of gene sequences to eliminate — or introduce — specific properties in an organism is not a new development. It has been happening for several decades now, particularly in the field of agriculture, where genetically modified variants, with specific desirable traits, are regularly developed. It usually involves the introduction of a new gene, or suppression of an existing gene, through a process described as genetic engineering.

CRISPR technology is different. It is simple, and still far more accurate — and it does not involve the introduction of any new gene from the outside. Its mechanism is often compared to the ‘cut-copy-paste’, or ‘find-replace’ functionalities in common computer programmes. A bad stretch in the DNA sequence, which is the cause of disease or disorder, is located, cut, and removed — and then replaced with a ‘correct’ sequence. And the tools used to achieve this are not mechanical, but biochemical — specific protein and RNA molecules.

The technology replicates a natural defence mechanism in some bacteria that uses a similar method to protect itself from virus attacks.

Technology in action

The first task is to identify the particular sequence of genes that is the cause of the trouble. Once that is done, an RNA molecule is programmed to locate this sequence on the DNA strand, just like the ‘find’ or ‘search’ function on a computer. After this, a special protein called Cas9, which is often described as ‘genetic scissors’, is used to break the DNA strand at specific points, and remove the bad sequence.

A DNA strand, when broken, has a natural tendency to re-attach and heal itself. But if the auto-repair mechanism is allowed to continue, the bad sequence can regrow. So, scientists intervene during the auto-repair process by supplying the correct sequence of genetic codes, which attaches to the broken DNA strand. It is like cutting out the damaged part of a long zipper, and replacing it with a normally functioning part.

The entire process is programmable, and has remarkable efficiency, though chances of error are not entirely ruled out.

Possibilities it presents

A vast number of diseases and disorders are genetic in nature — that is, they are caused by unwanted changes or mutations in genes. These include common blood disorders like sickle cell anaemia, eye diseases including colour blindness, several types of cancer, diabetes, HIV, and liver and heart diseases. Many of these are hereditary as well. This technology opens up the possibility of finding a permanent cure to many of these diseases.

This is also true for the deformities arising out of abnormalities in gene sequences, like stunted or slow growth, speech disorders, or inability to stand or walk.
Also, CRISPR is just a platform; a tool to edit gene sequences. What is to be edited, and where, is different in different cases. Therefore, a specific solution needs to be devised for every disease or disorder that is to be corrected. The solutions could be specific to particular population or racial groups, since these are also dependent on genes.

CRISPR-based therapeutic solutions are not in the form of a pill or drug. Instead, some cells of every patient are extracted, the genes are edited in the laboratory, and the corrected genes are then re-injected into the patients.

Over the last three years, several such solutions have been undergoing clinical trials. These mainly pertain to blood disorders, diabetes, inherited eye diseases, and some kinds of cancers. The case of Victoria Gray, suffering from sickle cell anaemia, who was in the first batch of patients who were treated using CRISPR-based solutions, has been widely tracked. Gray is now considered cured of the disease. Several others who volunteered with her for the trials too have responded positively to the treatment.

In India, Debojyoti Chakraborty and Souvik Maiti at CSIR’s Institute of Genomics and Integrative Biology have indigenously developed a CRISPR-based therapeutic solution for sickle cell anaemia, which is now being readied for clinical trials.

“We are just starting the pre-clinical phase (trials on animal subjects). It would take about two to three years to reach clinical trial stage. This is the first disease that is being targeted for CRISPR-based therapy in India,” Chakraborty said.

Japan has already approved the commercial cultivation of a tomato variety that has been improved using CRISPR-based intervention. In India, several research groups are working on CRISPR-based enhancements for various crops including rice and banana.

The ethical dilemma

Because of CRISPR’s power to induce dramatic changes in an individual, scientists, including the main developer Doudna, have been warning of the potential for misuse of the technology.

In 2018, a Chinese researcher disclosed that he had altered the genes of a human embryo to prevent the infection of HIV. This was the first documented case of creating a ‘designer baby’, and it caused widespread concern in the scientific community.

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Preventive interventions to obtain special traits is not something that scientists currently want the technology to be used for. Also, because the changes were made in the embryo itself, the new acquired traits were likely to be passed to future generations. Though the technology is fairly accurate, it is not 100 per cent precise, and could induce a few errors as well, making changes in other genes. This has the possibility of being inherited by successive generations.

In case of therapeutic interventions, the changes in genetic sequences remain with the individual and are not passed on to the offspring.

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