Page 9 - Biotechnology newsletter 2023-24

CRISPR-Cas9: A Promising Frontier in Treating Sickle
Cell Anemia

CRISPR ( Clustered Regularly Interspaced Short Palindromic Repeats ) is a revolutionary
gene-editing technology that allows scientists to precisely modify DNA. Originally derived
from a bacterial defense mechanism against viruses, CRISPR has been adapted for use in
various fields, including medicine, agriculture, and biotechnology. CRISPR-Cas9, the first
generation of CRISPR technology, consists of a guide RNA that directs the Cas9 enzyme to
specific locations in the genome, where it can cut the DNA. This enables researchers to edit
genes by introducing new genetic material or repairing existing mutations.
Since the development of CRISPR-Cas9, researchers have continued to refine and improve
the technology, leading to what is sometimes referred to as “CRISPR 2.0” or “next-
generation CRISPR.” This includes advancements such as; enhanced precision, with improved
specificity and reduced off-target effects; Expanded capabilities such as Cas12 and Cas13
development, which offer different targeting and editing abilities and allows more precise
changes to individual DNA bases without causing double-strand breaks, reducing the risk of
unintended mutations. These advancements have expanded the potential applications of
CRISPR technology and have led to exciting possibilities for treating genetic diseases,
engineering crops with desirable traits, and understanding the fundamental mechanisms of
biology.
In recent years, CRISPR is prominently used for the treatment of Sickle Cell Disease. Sickle
cell disease is a group of inherited blood disorders. Sickle cell anemia is caused by a single
point mutation in the hemoglobin, a protein found in red blood cells that delivers oxygen to
the body’s tissues. This mutation causes red blood cells to develop a “sickle” shape. These
sickled red blood cells restrict the flow in blood vessels and limit oxygen delivery to the
body’s tissues, leading to severe pain and organ damage called Vaso-occlusive events
(VOEs) or Vaso-occlusive crises (VOCs).
Casgevy and Lyfgenia, representing the first cell-based gene therapies for the treatment of
sickle cell disease (SCD) in patients 12 years and older, which is approved by FDA. Casgevy is
the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology.
Patients’ hematopoietic (blood) stem cells are modified by genome editing using
CRISPR/Cas9 technology. CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling
the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified
blood stem cells are transplanted back into the patient where they engraft (attach and
multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a
type of hemoglobin that facilitates oxygen delivery. Lyfgenia is a cell-based gene therapy.
Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification and is
approved for the treatment
But how does CRISPR is used to treat sickle cell anemia?
It’s simple. By targeting the Mutation. CRISPR can be used to specifically target the mutated
hemoglobin gene sequence in the patient’s DNA. Once the mutated sequence is targeted,
CRISPR can facilitate the insertion of a corrected DNA sequence at that location. This
corrected sequence would produce normal hemoglobin instead of the faulty version. CRISPR
components, including the guide RNA and Cas9 enzyme, need to be delivered into the
patient’s cells. This can be done using various delivery methods, such as viral vectors or
nanoparticles.
~Siya Raut
S.Y.B.Sc Biotechnology
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