CRISPR Cas9 Gene Therapy for Sickle Cell Disease

Why in the News?

India is close to developing a gene therapy using CRISPR-Cas9, a gene-editing tool for sickle cell disease (SCD).
- SCD is a genetic blood disorder prevalent among the Scheduled Tribes.

Sickle cell disease (SCD) is a group of inherited blood disorders caused by a genetic mutation in the hemoglobin-β gene located on chromosome 11.
This mutation results in defective hemoglobin, which forms rod-like structures after releasing oxygen.
As a result, red blood cells become rigid and assume a sickle shape.
The disease is inherited in an autosomal recessive pattern, meaning both parents must carry the abnormal gene for a child to inherit it.
Symptoms may not manifest immediately in newborns but can include extreme tiredness, fussiness, swollen hands and feet, and jaundice.

- - The mis-shapen RBCs can block small blood vessels, leading to impaired blood flow and causing chronic anaemia.
  - Individuals with SCD often experience acute pain episodes, severe bacterial infections, and tissue damage due to inadequate blood supply.

- Presently treatment includes medications for pain relief, regular blood transfusions to replace damaged red blood cells.
- In rare cases, a bone marrow or stem cell transplant, which carries significant risks, is recommended.

This progress follows the approval of CRISPR-Cas9 technology by the U.S. Food and Drug Administration for a cell-based gene therapy to treat sickle cell disease in December 2023.
One of the main challenges for India is to develop a cost-effective therapy, as part of its mission to eradicate sickle cell disease by 2047, launched by Prime Minister in July 2023.
The mission aims to conduct over 7 crore screenings among vulnerable tribal populations across 17 States and Union Territories, with three crore screenings completed so far.

CRISPR-Cas9 stands for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9.
It is a technology that allows geneticists and researchers to edit parts of the genome by altering sections of the DNA sequence.
Emmanuelle Charpentier and Jennifer Doudna’s work on CRISPR-Cas9 as a ‘molecular scissor’ earned them the 2020 Nobel Prize in chemistry.
The system consists of two key components:

Cas9: This is the enzyme that acts like a pair of molecular scissors. It is responsible for cutting the DNA strand at a specific location, allowing for the removal, addition, or alteration of DNA at that site.
Guide RNA (gRNA): This is a piece of RNA that is designed to find and bind to a specific sequence of DNA that matches its code. The gRNA guides the Cas9 enzyme to the exact spot in the genome where an edit is desired.

Mechanism:
- The process begins with the design of a gRNA that matches the DNA sequence where an edit is needed.
- Once inside the cell, the Cas9 enzyme and the gRNA form a complex that can identify and bind to the target DNA sequence.
- The Cas9 then cuts the DNA at this location.
- After the DNA is cut, the cell’s natural repair mechanisms can be harnessed to add or remove genetic material, or to make specific changes to the DNA.

[2023] Consider the following statements in the context interventions being undertaken under Anaemin Mukt Bharat Strategy :

It provides prophylactic calcium supplementation for pre-school children, adolescents and pregnant women.
It runs a campaign for delayed cord clamping at the time of child-birth.
It provides for periodic deworming to children and adolescents.
It addresses non-nutritional causes of anaemia in endemic pockets with special focus on malaria, hemoglobinopathies and fluorosis.

How many of the statements given above are correct?

(a) Only one
(b) Only two
(c) Only three
(d) All four