- A research team from The Institute of Basic Science utilized pre-assembled
CRISPR complex called Cas9 ribonucleoprotein
- This pre-assembled complex modified the VEGF gene locally and
degenerated within 72 hours
- Potential treatment for age related macular degeneration identified
have developed a gene surgery in the tissue layer supporting the retina which
promises to be a potential form of therapy for patients with age related
macular degeneration. Among people over the age of 65 years, one in 10 people
show signs of this condition, with its prevalence increasing with age. Age
related macular degeneration
(AMD) occurs commonly among Caucasians,
resulting in blind spots and vision distortion. The study published in the
journal Genome Research
is based on
laboratory studies as well as animal studies.
is a condition in which there is blood vessel damage in the retina. The retina
offers a view of the health of the circulatory system; it provides a glimpse of
the blood vessels of the body and can thus be used to detect early signs of
diabetes or high blood pressure complications. It is the inner layer of the eye
where the light received is changed into visual messages that are received by
‘CRISPR-Cas9 system can now be used to cure age related degenerative diseases and retinopathy through gene therapy.’
- 'Retinopathy of prematurity' - This is a potentially blinding disease that occurs
due to the abnormal retinal blood vessel development among premature
infants. There is a high risk for premature babies to have abnormal blood
vessel development. The condition may be resolved without damage being
caused to the retina but in severe cases, it could result in the retina
being pulled away and lead to permanent blindness.
- 'Hypertensive retinopathy'-
This type of retinopathy is caused due to high blood pressure. Normally,
this does not impair vision; however, blockage of retinal veins and
arteries could result in the loss of vision.
- 'Diabetic retinopathy'
- This type of retinopathy occurs due to the deterioration of the blood
vessels in the retina and can affect both eyes. People who have diabetes
for longer than 20 years are normally associated with retinal damage;
retinopathy is the major cause of blindness in North America.
macular degeneration' - This type of
retinopathy affects older adults and is caused by the deterioration of the
central portion of the retina called the macula.
the different types of retinopathy, there are abnormal levels of the vascular
endothelial growth factor (VEGF)
which are secreted. In age related macular
degeneration, VEGF aids in the formation of new blood vessels which causes the
leakage of blood as well as fluid into the eye, resulting in damage to the
most widely used treatment for age related macular degeneration is injections
with anti-VEGF drugs. The main drawback of this method of treatment is that
since vascular endothelial growth factors (VEGF) are over expressed by the
retinal pigment epithelial cells, at least 7 injections may be required every
year. Dr. Kim Jin-Soo who is the Director of the Center of Engineering at the
Institute of Basic Science (IBS) said that these anti-VEGF injections do not
address the main problem of the disease but only its effects.
avoid such invasive procedures the research team from The Institute of Basic
Science decided to use the CRISPR-Cas9 system to provide a third generation
gene therapy solution. Dr. Kim further detailed that editing the VEGF gene
would provide a long term cure.
CRISPR-Cas9 for Gene
CRISPR-Cas9 gene editing tool
can be used to
precisely cut and correct desired strands of DNA in the genome. This gene
editing tool cuts inside the VEGF gene and earlier studies conducted by the
research team showed that
- Cas9 ribonucleoprotein
(RNP) which is a pre-assembled variant of CRISPR-Cas9, could be used to
deliver stem cells to change genes that are being targeted.
- The assembled
variant works fast and then degrades quickly before an immune response is
mounted by the host body.
there are many advantages in using this procedure, the hurdles involved in the
delivery of these pre-assembled complexes have limited its use in therapeutics.
Injection of the
CRISPR-Cas9 into the Eyes
research team injected the CRISPR-Cas9 into the eyes of mice with wet age
related macular degeneration which resulted in the modification of the VEGF
gene. The findings of the study were
- The pre-assembled
CRISPR-Cas9 complex's delivery is more efficient that of the gene editing
tool complex in a plasmid form.
- In a period of 72
hours, the complex dissolved.
- When the entire
genome was assessed by the research team, the CRISPR-Cas9 complex was
found to have modified only the VEGF gene but not any other gene.
neovascularization (CNV) (the creation of new blood vessels) was monitored
to understand the progression of the disease. There was reduction in CNV
- Cone dysfunction
is a possible side effect of age related macular degeneration which
usually occurs within 3 days in these mice; in this treatment method it
did not occur even a week later.
CRISPR-Cas9 system has always been used in the treatment of hereditary
diseases. However, the current study showed that even degenerative diseases
that were non-hereditary could be corrected without the risk of affecting other
first human trial of the CRISPR-Cas9 system was conducted on patients with lung
cancer last year with a potential for use among people with sickle cell anemia
and other forms of hereditary diseases. The current study offers hope for
treatment of diseases that occur due to increased age, which could increase the
quality of life of older people.
- Retinopathy of Prematurity - (https://www.aapos.org/terms/conditions/94)
- Diabetic Retinopathy - (http://care.diabetesjournals.org/content/26/suppl_1/s99)