The gene-editing technology, CRISPR (clustered regularly interspaced short palindromic repeats) has been a breakthrough solution for many health problems in recent years. CRISPR has almost unlimited potential and has produced many flawless results in many clinical trials. Therefore, Indian government has also approved a five-year project to develop CRISPR to cure thalassaemia or sickle cell anaemia which has mainly been afflicting the tribal populations of the country. (Thalassaemia is an inherited blood disorder due to non-production of sufficient haemoglobin. The disease is passed from parents to children but can be treated and well-managed with blood transfusions and chelation therapy.)
Significance of CRISPR
Ever since the COVID-19 pandemic, humans have become vulnerable to many new diseases, around the world. For the past 10 years, scientists have made many breakthroughs by utilising this technology. Moreover, they are very optimistic on permanent cures to some of the most intractable health disorders since this technology has begun to deliver great results including improvement in the quality of human life.
Several therapeutic interventions have been performed using CRISPR for diseases such as thalassaemia over the past three years. In the US, the initial clinical trial results have been flawless. This technology enables a simple but remarkably efficient way to edit the genetic codes of living organisms. Thus, it has opened up the possibility of correcting genetic information to cure diseases, prevent physical deformities or even produce cosmetic enhancements. Now, the international focus is on developing a range of specific solutions to various ailments using CRISPR. In 2021, the Indian government also approved a five-year project to develop this technology to cure thalassaemia. Besides thalassaemia, there are many diseases caused due to genetic disorders, i.e., unwanted changes or mutations in genes, such as eye diseases including colour blindness, various types of cancer, diabetes, HIV, liver, and heart diseases. Many such diseases are hereditary as well. The CRISPR technology can possibly find a permanent cure to many such diseases.
About CRISPR Technology
CRISPR is a reference to the clustered and repetitive sequences of the DNA found in bacteria. This gene-editing technology replicates the natural mechanism of bacteria to fight some viral diseases. The CRISPR technology was developed by Jennifer Doudna and Emmanuelle Charpentier, who won the Nobel Prize for Chemistry in 2020.
The CRISPR technology is not a new development altogether; it is simple, far more accurate, and does not involve the introduction of any new gene from the outside. In this technology, a bad stretch in the DNA sequence, which is the cause for the disease or disorder, is located, cut, and removed. Thereafter, the bad stretch is replaced with a correct sequence. All this is done through a biochemical process using a specific protein and RNA molecules.
CRISPR is a platform for editing gene sequences—what is to be edited, and where, it varies from case to case. Hence, tailor-made solutions are devised for every disease or disorder which needs to be corrected. The solutions are gene-based, so they could be specific to particular population or radical groups.
How CRISPR Works
First of all, the particular sequence of genes, which is the cause for the trouble, is identified. Thereafter, an RNA molecule is programmed to locate this sequence on the DNA strand. For this purpose, scientists engineer a piece of RNA that is a match for the DNA that requires editing. This RNA is called the guide RNA. After that, a special protein, called Cas9, often described as ‘genetic scissors’, is used to break the DNA strand at specific points and remove the bad sequence. The Cas9 binds to the piece of DNA and temporarily unwinds a section of the DNA. After cutting, the DNA strand naturally re-attaches and heals itself.
However, if the auto-repair mechanism is allowed to continue, a bad sequence could also regrow. Therefore, scientists intervene during the auto-repair process by supplying the correct sequence of genetic codes, which attach to the broken DNA strand. Machinery inside the cell rushes to fix the broken DNA. This process uses similar-looking, unbroken pieces of DNA as a template to stitch broken pieces together. Thus, tailor-made DNA could be put in the cell, tricking machinery into using engineered DNA as template. Though this entire process is programmable and has shown remarkable efficiency, chances of error cannot be entirely ruled out.
Clinical trials for several such solutions are being conducted since the past three years. For instance, the case of a patient, Victoria Gray, who has been suffering from sickle cell anaemia, was in the first batch of patients who are treated using CRISPR-based solutions. Her recovery process has been tracked widely and she is not considered cured of the disease.
CRISPR in India
In India, Debojyoti Chakraborty and Souvik Maiti [Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology] have indigenously developed a CRISPR-based therapeutic solution for thalassaemia, which is now being getting ready for clinical trials in about two to three years and would be the first disease that is being targeted for CRISPR-based therapy in India.
Ethical Precaution
In view of the power to induce dramatic changes in an individual, scientists have warned that there could be potential misuse of CRISPR technology. In 2018, a Chinese researcher had 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’ which caused widespread concern in the scientific community. Scientists do not want to use CRISPR technology for obtaining special traits. Also, since the changes were made in the embryo itself, the new acquired traits may pass on to future generations. Though fairly accurate, if a few errors are induced while editing genes, the changes may be inherited by successive generations. However, if it is used in therapeutic interventions, the changes remain with the individual only.
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