Eight Diseases CRISPR Technology Could Cure
labiotech.eu/best-biotech/crispr-technology-cure-disease
September 13, 2021
CRISPR technology offers the promise to cure any human genetic disease with
gene editing; which one will be the first?
CRISPR-Cas9 was first used as a gene-editing tool in 2012. In just a few years, the technology
has exploded in popularity thanks to its promise of making gene editing much faster,
cheaper, and easier than ever before.
CRISPR is short for ‘clustered regularly interspaced short palindromic repeats.’ The term
makes reference to a series of repetitive patterns found in the DNA of bacteria that form the
basis of a primitive immune system, defending them from viral invaders by cutting their
DNA.
Using this natural process as a basis, scientists developed a gene-editing technology called
CRISPR-Cas9 that can cut a specific DNA sequence by simply providing it with an RNA
template of the target sequence. This allows to then add, delete or replace elements within
the target DNA sequence.
This system represented a big leap from previous gene-editing technologies, which required
designing and making a custom DNA-cutting enzyme for each target sequence rather than
simply providing an RNA guide, which is much simpler to synthesize.
CRISPR gene editing has already changed the way scientists do research, allowing a wide
range of applications across multiple fields. But the technology could also hold great
potential as a treatment for human diseases. In theory, CRISPR could let us edit any genetic
mutation at will to cure any disease with a genetic origin. In practice, however, CRISPR is
still in the beginning stages of its therapeutic development.
Here is a list of some of the first diseases that scientists are tackling using CRISPR-Cas
technology, testing its possibilities and limits as a medical tool.
1. Cancer
China has been spearheading the first clinical trials using CRISPR-Cas9 as a cancer
treatment. One of these studies was testing the use of CRISPR to modify immune T cells
extracted from the patient. The gene-editing technology is used to remove the gene that
encodes for a protein called PD-1. This protein found on the surface of immune cells is the
target of some cancer drugs such as checkpoint inhibitors. This is because some tumor cells
are able to bind to the PD-1 protein to block the immune response against cancer.
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The trial tested this approach in 12 patients with non-small cell lung cancer at the West
China Hospital. The results, published in April 2020, suggested the approach was feasible
and safe.
However, a later article pointed out that the study revealed some of the technology’s
limitations, including variable efficiency in the genome-editing process. Some experts have
recommended that the long-term safety of the approach remain under review. Others have
suggested using more precise gene-editing approaches such as base editing.
In the US, a phase I trial run by the University of Pennsylvania tested the safety of a similar
approach. The researchers used CRISPR to remove three genes that help cancer cells evade
the immune system. They then added another gene to help the immune cells recognize
tumors. The results revealed that the treatment was safe in patients with advanced forms of
cancer.
Meanwhile, the company CRISPR Therapeutics is currently running a global phase I trial
that is expected to recruit over 130 patients with blood cancer to test a CAR-T cell therapy
made using CRISPR technology.
2. Blood disorders
The blood disorders beta-thalassemia and sickle cell disease, which affect oxygen transport in
the blood, are the target of a CRISPR treatment being developed by CRISPR Therapeutics
and its partner Vertex Pharmaceuticals.
The therapy consists of harvesting bone marrow stem cells from the patients and using
CRISPR technology in vitro to make them produce fetal hemoglobin. This is a natural form of
the oxygen-carrying protein that binds oxygen much better than the conventional adult form.
The modified cells are then reinfused into the patient.
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In December, preliminary results revealed that all five patients with thalassemia haven’t
required any blood transfusions since receiving the treatment, and the two patients with
sickle cell disease have so far not experienced any of the usual bleeding episodes caused by
their condition.
Hemophilia is another blood disorder that CRISPR technology could tackle, although
development is still at the preclinical stage. CRISPR Therapeutics is working with Casebia on
an in vivo CRISPR therapy where the gene-editing tool is delivered directly to the liver. Last
year, Intellia Therapeutics and Regeneron Pharmaceuticals teamed up to pursue the
development of hemophilia treatments based on genome editing.
3. Blindness
Many hereditary forms of blindness are caused by a specific genetic mutation, making it easy
to use CRISPR-Cas9 to treat it by targeting and modifying a single gene. In addition, the
activity of the immune system is limited in the eye, which can circumvent any problems
related to the body rejecting the treatment.
The company Editas Medicine is working on a CRISPR therapy for Leber congenital
amaurosis, the most common cause of inherited childhood blindness, for which there is
currently no treatment. The treatment aims to use CRISPR to restore the function of lightsensitive cells before the children lose sight completely by fixing the most common genetic
mutation behind the disease.
Last year the company started a phase I/II trial, with results expected by 2024. This is the
first trial to test an in vivo CRISPR treatment, in which the gene editing happens directly
inside the patient’s body rather than on cells extracted from their body and then returned to
it.
4. AIDS
There are several ways CRISPR could help us in the fight against AIDS. One is using CRISPR
to cut the viral DNA that the HIV virus inserts within the DNA of immune cells. This
approach could be used to attack the virus in its hidden, inactive form, which is what makes
it impossible for most therapies to completely get rid of the virus.
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Another approach could make us resistant to HIV infections. Certain individuals are born
with a natural resistance to HIV thanks to a mutation in a gene known as CCR5, which
encodes for a protein on the surface of immune cells that HIV uses as an entry point to infect
the cells. The mutation changes the structure of the protein so that the virus is no longer able
to bind to it.
This approach was used in a very controversial case in China two years ago in which human
embryos were genetically edited to make them resistant to HIV infections. The experiment
caused outrage among the scientific community, with some studies pointing out that the
‘CRISPR babies’ might be at a higher risk of dying younger. The general consensus seems to
be that more research is needed before this approach can be used in humans, especially as
recent studies have pointed out this practice can have a high risk of unintended genetic edits
in embryos.
5. Cystic fibrosis
Cystic fibrosis is a genetic disease that causes severe respiratory problems. Although there
are treatments available to deal with the symptoms, the life expectancy for a person with this
disease is only around 40 years. CRISPR technology could help us get to the origin of the
problem by editing the mutations that cause cystic fibrosis, which are located in a gene called
CFTR.
Last year, researchers in the Netherlands used base editing to repair CFTR mutations in vitro
in the cells of people with cystic fibrosis without creating damage elsewhere in their genetic
code. In addition, companies such as Editas Medicine, CRISPR Therapeutics, and Beam
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Therapeutics have plans to develop treatments for cystic fibrosis using CRISPR systems.
Cystic fibrosis can be caused by multiple different mutations in the target gene, however,
meaning that different therapies will have to be developed for different genetic defects.
Editas Medicine has stated that it will be looking at the most common mutations, as well as
some of the rare ones for which there is no treatment.
6. Muscular dystrophy
Duchenne’s muscular dystrophy is caused by mutations in the DMD gene, which encodes for
a protein necessary for the contraction of muscles. Children born with this disease suffer
progressive muscle degeneration, and existing treatments are limited to a fraction of patients
with the condition.
Research in mice has shown CRISPR technology could be used to fix the multiple genetic
mutations behind the disease. In 2018, a group of researchers in the US used CRISPR to cut
at 12 strategic ‘mutation hotspots’ covering the majority of the estimated 3,000 different
mutations that cause this muscular disease. A company called Exonics Therapeutics was
spun out to further develop this approach.
Editas Medicine is also working on a CRISPR therapy for Duchenne’s muscular dystrophy.
The company is following a broader approach where instead of fixing specific mutations,
CRISPR gene editing is used to remove whole sections of the mutated protein, which makes
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the protein shorter but still functional.
7. Huntington’s disease
Huntington’s disease is a neurodegenerative condition with a strong genetic component. The
disease is caused by an abnormal repetition of a certain DNA sequence within the huntingtin
gene. The higher the number of copies, the earlier the disease will manifest itself.
Treating Huntington’s could be tricky, as any off-target effects of CRISPR in the brain could
have very dangerous consequences. To reduce the risk, scientists are looking at ways to tweak
the genome-editing tool to make it safer.
In 2018, researchers at the Children’s Hospital of Philadelphia revealed a version of CRISPRCas9 that includes a self-destruct button. A group of Polish researchers opted instead for
pairing CRISPR-Cas9 with an enzyme called nickase to make the gene editing more precise.
8. Covid-19
In the face of the Covid-19 pandemic, CRISPR has quickly been put to the use of making fast
screening tests. In the longer term, the gene-editing tool might allow us to fight Covid-19 and
other viral infections.
Scientists at Stanford University have developed a method to program a version of the geneediting technology known as CRISPR/Cas13a to cut and destroy the genetic material of the
virus behind Covid-19 to stop it from infecting lung cells. This approach has shown to reduce
the viral load in human cells by 90% and to work against 90% of all existing and emerging
coronaviruses.
Another research group at the Georgia Institute of Technology has used a similar approach to
destroy the virus before it enters the cell. The method was tested in live animals, improving
the symptoms of hamsters infected with Covid-19. The treatment also worked on mice
infected with influenza, and the researchers believe it could be effective against 99% of all
existing influenza strains.
The future of CRISPR technology
Considering that CRISPR-Cas9 is a relatively new development in the world of biology,
research has only begun to scratch the surface of the role it could play in the future of
medicine. The examples listed here are just the first attempts at using CRISPR technology as
a therapy. As they progress, we can expect more and more indications to be added to the list.
One of the biggest challenges to turn this research into real cures is the many unknowns
regarding the potential risks of CRISPR therapy. Some scientists are concerned about
possible off-target effects as well as immune reactions to the gene-editing tool. But as
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research progresses, scientists are proposing and testing a wide range of approaches to tweak
and improve CRISPR in order to increase its efficacy and safety.
Hopes are high that CRISPR-Cas9 technology will soon provide a way to target and destroy
complex diseases such as cancer and AIDS, and even target genes associated with mental
illnesses.
Images via NIH /Flickr; Shutterstock. This article was originally published in June 2018
and has since been updated to reflect the latest developments in CRISPR research.
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