U.S. FDA approves pair of gene therapies for sickle cell disease

Subject: Science and Tech

Section: Biotechnology

Context:

The U.S. Food and Drug Administration (FDA) approved a pair of gene therapies for sickle cell disease, including the first treatment based on the breakthrough CRISPR gene editing technology.

Key details:

The agency approved Lyfgenia from bluebird bio, and a separate treatment called Casgevy by partners Vertex Pharmaceuticals and CRISPR Therapeutics for the illness.
Both the therapies were approved for people aged 12 years and older.
The Vertex/CRISPR gene therapy uses the breakthrough gene editing technology that won its inventors the Nobel Prize in 2020.
Makers of both the therapies have pitched them as one-time treatments, but data on how long their effect lasts is limited.
The only longer-term treatment for sickle cell disease is a bone marrow transplant.

Sickle cell disease:

Sickle cell disease (SCD) is a group of inherited red blood cell disorders.
Red blood cells contain hemoglobin, a protein that carries oxygen.
Healthy red blood cells are round, and they move through small blood vessels to carry oxygen to all parts of the body.
SCD, causes the red blood cells to become hard and sticky and look like a C-shaped farm tool called a “sickle.”
The sickle cells die early, which causes a constant shortage of red blood cells.
Also, when they travel through small blood vessels, they get stuck and clog the blood flow.
This can cause pain and other serious complications (health problems) such as infection, acute chest syndrome and stroke.

What is CRISPR?

CRISPR is a powerful tool for editing genomes.
It allows researchers to easily alter DNA sequences and modify gene function.
It has many potential applications, including:correcting genetic defects, treating and preventing the spread of diseases, and improving the growth and resilience of crops.
“CRISPR” is shorthand for “CRISPR-Cas9.”
CRISPRs are specialized stretches of DNA, and the protein Cas9 (where Cas stands for “CRISPR-associated“) is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA.
CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea, a domain of relatively simple single-celled microorganisms.
These organisms use CRISPR-derived RNA to foil attacks by viruses.
When the components of CRISPR are transferred into more complex organisms those components can then manipulate genes, a process called “gene editing.” How CRISPR works as a genome-editing tool

About Casgevy:

Casgevy is a gene therapy that utilises the gene-editing tool CRISPR.
The process works by taking the patient’s bone marrow stem cells and editing them to express the fetal version of haemoglobin before transplanting these edited stem cells back into the patient.
Fetal haemoglobin is the version expressed in utero, before birth.
In most people, expression of the fetal version is turned down and the non-fetal version is turned on when they are a baby, although there is still usually a very small amount of fetal haemoglobin expressed.
Casgevy edits this by turning up the expression of the fetal version.
The functional haemoglobin produced from this version of the gene compensates for the non-functional haemoglobin that the non-fetal version of the gene is producing.
The edited stem cells are the patient’s own cells, just slightly edited, and as such there is no risk of rejection.
The results have the potential to be life-long.

About Lyfgenia:

Lyfgenia is a cell-based gene therapy.
Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification and is approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events.
With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by sickle cell disease.
Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow.
These modified stem cells are then delivered to the patient.