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CRISPR UPSC NOTE

 Sickle cell anemia basic details

  • Sickle cell anemia (SCA) is a genetic blood disorder characterized by abnormal red blood cells

  • These cells, instead of being smooth and disc-shaped, deform into a sickle-like shape under certain conditions.

What causes it?

  • SCA is caused by inheriting two copies of a mutated hemoglobin gene, one from each parent. 

  • Hemoglobin is the protein in red blood cells responsible for carrying oxygen throughout the body.

  • OthercomplicationsFrequent infections, delayed growth, organ damage (e.g., spleen, liver, lungs), and stroke are potential complications.

CRISPR-based gene editing technology in the context of treating genetic diseases like sickle cell anemia

  • Casgevy and Lyfgenia, the two cell-based gene therapies approved by the Food and Drug Administration (FDA) for sickle cell anemia treatment and beta-thalassemia utilise the Nobel-winning CRISPR/Cas 9 genome editing technology.

  • Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), a feature of the bacterial immune system, forms the basis for this technology. 

  • In a nutshell, the system in bacteria serves as a warehouse for past infections by storing a part of the viral genetic material and incorporating it into its own.

  • So the next time it is attacked, the bacteria is capable of recognising the virus and destroying it. 

  • The bacteria, in short, is immunised when it employs the CRISPR system

  • The CRISPR-Cas system is effective and easy to manipulate. 

  • Researchers have adapted it as a tool to cut, delete, or add DNA sequences at precise locations, opening different windows to treat genetic disorders, develop drought-resistant plants, modify food crops, or experiment with de-extinction projects involving the woolly mammoth and the dodo.

  • Sickle-cell anemia (SCA) is an inherited disorder where red blood cells contort to a sickle or crescent shape because of defective hemoglobin, restricting its ability to carry oxygen

  • According to an articlepublished in the Indian Journal of Medical Research over 20 million people live with SCA in India and it is predominantly seen in the scheduled tribes (ST) and scheduled caste (SC) populations where the majority are economically backward.

  • Casgevy costs $ 2.2 million per patient to treat sickle-cell anemia. 

  • Indian researchers are working on indigenous treatment involving CRISPR genome editing to reduce the cost. 

Possibilities and ethical concerns surrounding revolutionary tool

  • Apart from the health equity and disparities associated with CRISPR, one of the biggest controversies has been about germline editing.

  • Most of the scientific community supports the use of CRISPR to treat monogenic diseases.

  • Germline editing is heritable and more complex and begs the question if it is even moral to subject an individual to heritable changes, even if it is to treat debilitating genetic conditions.

  • As of now, genome editing is restricted to somatic cells and there is a moratorium on germline editing. 

  • Chinese scientist He Jiankui took the scientific world by storm when he announced that he had edited healthy embryos in an attempt to minimise girls’ predisposition to HIV infection.

  • This was in 2018 despite having guidelines against germline editing and at a time when studies had no clear-cut answers to the outcome of such an intervention

  • We still fully do not understand the long-term effects of CRISPR editing.

  • It’s not a technology which is absolutely 100% full-fledgedly understood

  • Guidelines, laws, and dialogues around ethical, societal, and safety issues need to evolve parallelly as technology evolves. 

  • Most countries including India have forbidden genome editing in human embryos through legal instruments or through guidelines. 

  • In India every Institution involved in biomedical research is required to follow ICMR National Ethical Guidelines and register with the ethics committee which monitors research (including around gene editing)”, said Dr. Mathur.

  • The gene editing technology has also raised concerns regarding it becoming a commodity that wealthy parents will exploit to improve the fate of their children not only for therapeutic purposes but for genetic enhancement. 

  • There is a chance that if we do not have a way to distribute these therapies to different parts of the world where it is needed through whatever mechanism, then you would have a division in the world because the therapy is there but the affordability isn’t there.

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