Casgevy and Lyfgenia: CRISPR-Based Gene Therapies

GS Paper III Science and Technology

Context:

Casgevy and Lyfgenia, the first CRISPR-based gene therapies have received approval from the Food and Drug Administration (FDA) for sickle cell anemia and beta-thalassemia treatment.

Casgevy™ made by Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia™, by Bluebird Bio—is for people 12 and older.
- These two therapies work in different ways however both therapies utilise the Nobel-winning CRISPR/Cas 9 genome editing technology.
What Is Casgevy Therapy?
- The therapy uses the patient’s blood stem cells, which are precisely edited using Crispr-Cas9.
- The therapy targets a gene called BCL11A, which is crucial for switching from fetal to adult haemoglobin.
- The therapy uses the body’s mechanisms to produce more foetal haemoglobin, alleviating the symptoms of the two conditions
What is Lyfgenia Therapy?

- It uses a viral envelope to deliver a healthy hemoglobin-producing gene.
- Lyfgenia works by taking a piece of a virus (a lentivirus, which belongs to the HIV family) and using it to deliver a functional version of a haemoglobin-producing gene.

Technique to replace defective genes with healthy genes to treat genetic disorders.
Artificial method that introduces DNA into the cells of the human body.
First developed in 1972, but has limited success.
There are two Major types of gene therapy: Somatic gene therapy and germline gene therapy.

Gene editing is a technique of making specific changes to the DNA at a specific sequence.
For this DNA is inserted, deleted, modified or replaced in the genome.
For this CRISPR CAS9 (Genetic Scissor) is used.
It involves cutting specific DNA sequences with ‘engineered nucleases’ enzymes.

It refers to the process in which the DNA of reproductive cells (such as sperm and eggs) or embryos are modified.
While somatic cell editing impacts only the treated individual, germline editing can lead to genetic changes for future generations.

Genetic Disorder: The genetic error in sickle cell disease leads to red blood cells assuming a crescent shape.
- Unlike the disc-shaped normal cells, the sickle-like cells cannot move around easily in the vessels, resulting in blocked blood flow.
Symptoms: severe pain, life-threatening infections, anaemia, or a stroke.
The symptoms manifest in people who inherit a pair of damaged genes from both parents. Those who carry only one copy of the gene from one parent can lead a normal life.
Prelevance in India: An estimated 30,000-40,000 children in India are born with the disorder every year.

Casgevy and Lyfgenia

It is also an inherited (i.e., passed from parents to children through genes) blood disorder caused when the body doesn’t make enough of a protein called haemoglobin.
Symptoms: Thalassaemia leads to low levels of haemoglobin and shows symptoms like fatigue, nausea, shortness of breath, and irregular heartbeats.
Prelevance in India: India also has the largest number of children with thalassaemia major in the world about 1-1.5 lakh.
Available Treatment: People with the condition need blood transfusions. The transfusions also lead to excess iron accumulation in the body, which needs chelation.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.
It’s found in bacteria and archaea, which are simple organisms.
- These sequences come from pieces of viruses that have attacked the organisms before.
CRISPR helps the organisms recognise and fight off similar viruses in the future.
CRISPR acts like an immune system. CRISPR helps the organisms recognise and fight off similar viruses in the future.

Casgevy and Lyfgenia

New Drugs and Clinical Trials Rules (2019): CRISPR research in India is governed by strict regulations, with Gene Therapy Products (GTPs) classified as new drugs under the New Drugs and Clinical Trials Rules (2019).
Central Drugs Standard Control: This organisation approves CRISPR.
Review Committee on Genetic Manipulation (RCGM)/Genetic Engineering Approval Committee (GEAC): Besides existing regulations, additional rules might be set based on national GTP guidelines and reviewed by relevant committees.
- Further requirements depend on national Gene Therapy Product guidelines and committee oversight.
The Indian Council of Medical Research (ICMR): All biomedical research in India requires ethical approval following ICMR guidelines (2017).
- India mandates ethical conduct for all biomedical research involving human participants (ICMR, 2017).

News Source: The Hindu

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