News Excerpt:
The U.S. The Food and Drug Administration (FDA) approves two gene therapies for sickle cell, bringing hope to thousands with the disease.

About Gene Therapies:

• CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel), the first two gene therapies for the treatment of sickle cell disease in patients 12 years and older with recurrent vaso-occlusive crises (VOCs). 
• FDA approved LYFGENIA, manufactured by Bluebird Bio, and CASGEVY, manufactured by partners Vertex Pharmaceuticals and CRISPR Therapeutics.
• The Vertex-CRISPR therapy has a U.S. list price of $2.2 million, while Bluebird's is $3.1 million. Both therapies, pitched as one-time treatments, will be available in early 2024.
• Casgevy is based on CRISPR which uses molecular "scissors" to trim faulty parts of genes that can be disabled or replaced with new strands of normal DNA.
• For Vertex's therapy, patients must have stem cells harvested from their bone marrow. 
• The cells are then sent to manufacturing facilities and edited using CRISPR/Cas9 technology. 
• Once the cells are incubated, they are infused back into the patient during a month-long hospital stay.
• Lyfgenia uses a more conventional form of gene therapy that uses a virus to ferry a gene into cells. 
• It uses a lentiviral vector (gene delivery vehicle) for genetic modification. 
• The patient’s blood stem cells are genetically modified to produce a gene-therapy derived hemoglobin that functions similarly to the normal adult hemoglobin produced in persons not affected by sickle cell disease. These modified stem cells are then delivered to the patient. 

What is Sickle Cell Disease?

• Sickle cell disease is a group of inherited red blood cell disorders that affect haemoglobin, the protein that carries oxygen through the body. 
• Red blood cells are generally disc-shaped and flexible enough to move easily through the blood vessels. 
  • In sickle cell disease, red blood cells become crescent- or "sickle"-shaped due to a genetic mutation. These sickled red blood cells do not bend or move easily and can block blood flow to the rest of the body.
• The blocked blood flow can lead to serious problems, including stroke, eye problems, infections, and episodes of pain called pain crises.
• This also leads to severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs). 
  • A vaso-occlusive crisis, or VOC, occurs when sickled red blood cells block blood flow to the point that tissues become deprived of oxygen. This in turn sets in motion an inflammatory response as the body tries to rectify the problem.
• Sickle cell disease is a lifelong illness. A bone marrow transplant is currently the only cure for sickle cell disease.

What is CRISPR Technology?

• CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) are short DNA sequences found in the genome of prokaryotic organisms such as bacteria, which are reminders of previous bacteriophage (viruses) attacks that the bacteria successfully defended against. 
• Cas9 (CRISPR-associated protein 9) enzyme (part of bacteria's defence mechanism) uses these flags to target and cut any foreign DNA precisely, thus protecting the bacteria from future attacks by similar bacteriophages. 
• The unprecedented precision of targeting the DNA sequences and then efficiently cutting them is the basis for CRISPR-Cas9 technology, recently demonstrated in editing genes in cells and organisms.
• CRISPR-Cas9 technology has been successfully used for many purposes, including basic studies of gene function, agriculture, and medicine to increase our knowledge of disease processes and their potential future therapies. So far, most binding trials were typically performed at 37 °C.

Prelims PYQ

Q. What is Cas9 protein that is often mentioned in news? (UPSC 2019)

(a) molecular scissors used in targeted gene editing.

(b) biosensor used in the accurate detection of pathogens in patients.

(c) gene that makes plants pest-resistant.

(d) herbicidal substance synthesized in genetically modified crops.