Over the past two and a half years, as the coronavirus pandemic has ravaged the world and exposed human vulnerabilities to new diseases, scientists have continued to move forward with significant advances in the use of exciting recent technology. for permanent cures to some of the toughest health problems. troubles.
In the 10 years since its development, the genome-editing technology called CRISPR has begun to realize the nearly limitless potential that scientists say it has for improving the quality of human life.
The technology offers a simple yet remarkably effective way to “modify” the genetic codes of living organisms, opening up the possibility of “correcting” genetic information to cure disease, prevent physical deformities, or even produce cosmetic enhancements.
In the last three years in particular, several therapeutic interventions using CRISPR for diseases like thalassemia or sickle cell disease have been the subject of clinical trials, mainly in the United States, and the first results have been flawless.
Last year, the Indian government approved a five-year project to develop this technology to cure sickle cell anemia which mainly affects tribal people in the country.
And that’s just the beginning. Hundreds of research groups and companies around the world are working to develop a range of specific solutions using CRISPR. The technology’s developers, Jennifer Doudna and Emmanuelle Charpentier, won the 2020 Nobel Prize in Chemistry, one of the earliest recognitions granted by the Nobel committee after a breakthrough.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which refers to the clustered and repetitive DNA sequences found in bacteria, whose natural mechanism to fight certain viral diseases is reproduced in this gene editing tool.
Editing or modifying gene sequences to eliminate – or introduce – specific properties into an organism is not a new development. This has been happening for several decades now, especially in the field of agriculture, where genetically modified variants, with specific desirable traits, are regularly developed. This usually involves the introduction of a new gene or the deletion of an existing gene, through a process called genetic engineering.
CRISPR technology is different. It’s simple, and still much more precise – and it doesn’t involve introducing a new gene from outside. Its mechanism is often compared to the “cut-copy-paste” or “find-and-replace” features of common computer programs. A bad stretch in the DNA sequence, which is the cause of a disease or disorder, is located, cut and removed, then replaced with a “correct” sequence. And the tools used to achieve this are not mechanical, but biochemical – specific proteins and RNA molecules.
The technology mimics a natural defense mechanism in certain 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 causing the problem. Once done, an RNA molecule is programmed to locate that sequence on the DNA strand, much like the “find” or “search” function on a computer. After that, a special protein called Cas9, which is often described as “genetic scissors”, is used to break the DNA strand at specific points and delete the bad sequence.
A strand of DNA, when broken, has a natural tendency to reattach and heal itself. But if the automatic repair mechanism is allowed to continue, the bad sequence can happen again. Thus, scientists intervene during the self-repair process by providing the correct sequence of genetic codes, which attaches to the broken DNA strand. It’s like cutting off the damaged part of a long zipper and replacing it with a part that works normally.
The whole process is programmable and has remarkable efficiency, although the risk of error is not entirely excluded.
Possibilities it presents
Many diseases and disorders are genetic in nature, that is, they are caused by unwanted changes or mutations in genes. These include common blood disorders such as sickle cell disease, eye diseases such as color blindness, several types of cancer, diabetes, HIV, and liver and heart disease. Many of them are also hereditary. This technology opens up the possibility of finding a permanent cure for many of these diseases.
This is also true for deformities resulting from abnormalities in genetic sequences, such as stunted or slow growth, speech impairment, or an inability to stand or walk.
Also, CRISPR is just a platform; a tool for editing gene sequences. What needs to be edited, and where, is different from case to case. Therefore, a specific solution must be designed for each disease or disorder to be corrected. Solutions could be specific to a particular population or racial groups, as these also depend on genes.
CRISPR-based therapeutic solutions do not come in pill or drug form. Instead, certain cells from each patient are extracted, the genes are modified in the laboratory, and the corrected genes are then injected back into the patients.
Over the past three years, several of these solutions have gone through clinical trials. These mainly relate to blood disorders, diabetes, inherited eye diseases and certain types of cancers. The case of Victoria Gray, who has sickle cell disease, who was among the first batch of patients treated with CRISPR-based solutions, has been widely followed. Gray is now considered cured of the disease. Several other people who volunteered with her for the trials also responded positively to the treatment.
In India, Debojyoti Chakraborty and Souvik Maiti of CSIR’s Institute of Genomics and Integrative Biology have locally developed a CRISPR-based therapeutic solution for sickle cell anemia, which is currently being prepared for clinical trials.
“We are just entering the preclinical phase (testing on animal subjects). It would take about two to three years to reach the stage of clinical trials. This is the first disease targeted by CRISPR-based therapy in India,” Chakraborty said.
Japan has already approved the commercial cultivation of a tomato variety that was improved through a CRISPR-based intervention. In India, several research groups are working on CRISPR-based improvements for various crops, including rice and banana.
The ethical dilemma
Because of CRISPR’s power to induce dramatic changes in an individual, scientists, including lead developer Doudna, have warned of the potential for misuse of the technology.
In 2018, a Chinese researcher revealed that he had altered the genes of a human embryo to prevent HIV infection. This was the first documented case of the creation of a “designer baby”, and it caused widespread concern in the scientific community.
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Preventative interventions to achieve special traits is not something scientists currently want the technology to be used for. Moreover, because the changes were made to the embryo itself, the newly acquired traits were likely to be passed on to future generations. Although the technology is quite precise, it is not 100% precise and could also induce some errors, by modifying other genes. This has the possibility of being inherited by successive generations.
In the case of therapeutic interventions, the changes in the genetic sequences remain with the individual and are not transmitted to the offspring.