- CRISPR gene
editing tool used to treat chronic
granulomatous disease by research team
The altered cells were introduced into the host where the
immune cells provided protection against bacteria
- The engineered
cells did not produce any side effect and remained in the system for 5
system is a gene editing tool that is used
to edit specific sequences of DNA and replace it with another sequence. This
system is now being used by scientists to correct mutations in the
hematopoietic stem cells to treat a rare immunodeficiency disorder called
chronic granulomatous disease (CGD).
The cells that were
engineered using this technology were grafted successfully into mice for a
period of 5 months. The success of the grafted engineered stem cell indicates
the potential application of the CRISPR-Cas9 system in the therapeutic
applications for inherited diseases.
‘Genetic disorders can soon be treated effectively using CRISPR-Cas9 system.’
Ex-Vivo Gene Therapy
The CRISPR-Cas9 system
could be useful in altering the mutations that are found to cause diseases,
with the alteration occurring in a laboratory and then implanting them back
into the body.
This allows selective isolation of the cells which need to
be altered and the CRSPR-Cas9 system can be controlled. Most often, the mutations that are
produced by the CRISPR-Cas9 system may be non-specific and lead to unwanted
mutations. However, carrying out these alterations in the genes in a controlled
setting could limit the risk for these unwanted mutations.
The use of CRISPR-Cas9
system has its fair share of flak due to the unintended mutations. A research
team lead by Dr. Suk See De Ravin and associates utilized this ex-vivo gene
editing approach that involved the use of this approach in the treatment of
. This is a genetic disorder with limited
treatment options that leads to life-threatening infections with the need for
antibiotics in the long run. It is caused due to a defect in the NOX2 protein,
a vital protein that is required by the immune system to destroy bacteria.
disease does not have a reliable treatment and, so, engineered stem cell
transplantation could offer a potential method of treatment. However, the use
of this gene editing system does hold a risk of lethal complications that could
result in toxicity.
The research team
- Repairing the NOX2
mutation that occur in the stem cells of patients with CGD
- Implanting these
cells into mice
- Showing their
ability to differentiate into immune cells with their anti-microbial
- The mice were able
to maintain these altered cells for a long period of time
- There were no
side effects that were noticed in the mice due to the implantation of
these altered cells
system has been found to show a lot of promise in the treatment of this
genetic disorder, it could soon be used for a gene based treatment
This system is a part of
an adaptive system that was developed in bacteria for immunity against virses
and plasmids. The Cas9 is an endonuclease which uses a guide that target
sequences, of DNA and induce a site-specific double-strand break in the DNA.
Doudna and colleagues who developed this method of gene editing, made necessary
changes to the target DNA which would then bind to the specific target DNA. The
CRISPR -Cas9 system was found to be simple and contained a unique DNA cleaving
mechanism with the capacity of target recognition that was multiplexed.
There are many naturally
existing CRISPR-Cas9 variants and they can be used for cost effective treatment
measures. It can be used to modify, target, edit and regulate a large amount of
genomic DNA loci across many cells and organisms.
This gene editing tool
has resulted in a complete revolution, providing a unique solution to many gene
system is used in functional genomics where the gene editing tool can be
used to identify drug targets and phenotypes that allow the generation of
cells that will benefit animal studies.
- Will enhance the
ability to insert target sequences into the host.
- Apart from human
diseases, CRISPR can also be used to develop new varieties of plants and aid in growing better quality crops.
- Scientists are
now trying to identify small molecules to the Cas9 system to make it
easier to deliver the system into humans.
The CRISPR-Cas9 system
has completely revolutionized gene therapy and the care that it can offer
patients with genetic diseases and with no line of treatment. The current study
that gene engineered cells could be successfully implanted into mice showed
that a promising treatment could soon be round the corner.
- Suk See De Ravin, Linhong Li, Xiaolin Wu, Uimook Choi, Cornell Allen, Sherry Koontz, Janet Lee, Narda Theobald-Whiting, Jessica Chu, Mary Garofalo, Colin Sweeney, Lela Kardava, Susan Moir, Angelia Viley, Pachai Natarajan, Ling Su, Douglas Kuhns, Kol A. Zarember, Madhusudan V. Peshwa, Harry L. Malech. CRISPR-Cas9 gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease. Science Translational Medicine, 2017; 9 (372): eaah3480 DOI: 10.1126/scitranslmed.aah3480