Biotechnology Genetics

CRISPR/Cas9: A Possible Cure For Down’s Syndrome

CRISPR gene editing technology has promised to revolutionize the treatment of genetic diseases including Down’s Syndrome. The disorders that once were considered unsolvable and incurable.

What Is Down’s Syndrome? 

Down’s syndrome is a chromosomal disorder in which a person instead of having 46 chromosomes, have 47 chromosomes. There is one extra chromosome number 21. It arises due to errors in cell division.

Types Of Down’s Syndrome

There are three types of Down’s syndrome;

  • 21st chromosome trisomy – an individual has one extra whole or partial 21st chromosome.
  • Mosaic Down’s syndrome – containing some of the cells are trisomy 21st, while other cells are normal.
  • Robertsonian Translocation – a part of the 21st chromosome breaks and joins with another chromosome.
CRISPR cure Down's Syndrome
The estimated incidence of Down syndrome is between 1 in 1,000 to 1 in 1,100 live births worldwide, according to the World Health Organization. Credit: Healthline

Also, there is a correlation between Down’s Syndrome with Pregnancies. It usually occurs in about in older pregnancies about 1 in every 700 over the age of 35. While over the age of 40, it is about 12 in 1000. So, as the age of mother increases, the rate/chances of a child having Down’s syndrome too.

Features of Down’s Syndrome

Down’s syndrome affects the life of an individual in a variety of ways like respiratory and hearing problems. Moreover, mental disabilities, childhood cancers and cognitive development problems. The classic feature of Down’s syndrome is facial features that include slanted eyes, short neck, flat nasal bridge.

Down’s Syndrome with Pregnancies
Shows the correlation of Down’s Syndrome with Pregnancies

Available Treatments for Down’s Syndrome

Currently, there is no such cure for Down Syndromes. However, ongoing therapies are given to individuals to reduce the severity of different problems. Also, early intervention can help to alleviate several issues and make it easier for a person to live with Down’s syndrome.

Moreover, we can prenatally screen for embryos having Down’s syndrome, and even chances are to correct them via pre-implantation genetic diagnosis and in-vitro fertilization. Nevertheless, we have no cure for this after birth.

What Is CRISPR Gene Editing Technology?

CRISPR is a novel gene editing tool that has the potential to edit or modify the genome of almost any organism.

Explore More: What Is CRISPR Cas9?

It is based on a bacterial defense system and evolved to fight against invading pathogens, mainly bacteriophages. CRISPR in bacteria recognizes the nucleic acid of these phage viruses. Cleave them at a specific site and then insert them into bacteria’s genome site called CRISPR locus. When the same phage attacks the bacteria, CRISPR will get activated and recognize the DNA sequence in phage genome and cleave it.

They are now utilizing the same target recognition ability. Scientists make CRISPR machinery, theoretically to target almost any target DNA, provided with its complementary sequences.

CRISPR
CRISPR-Cas9 has taken the world by storm in just a few years with the promise of making genome editing much easier and faster than ever before. Credit: Labiotech.eu

How CRISPR could be Use to Cure Down syndrome?

As the CRISPR has potential in targeting and editing that could be modified to cure Down’s Syndrome.

Here we have two options; either first somatically target doubled or copied genes for specific life-threatening traits on chromosome 21. Technically, using CRISPR to edit duplicated genes in somatic cells is currently impossible

Secondly, to completely eliminate the doubled 21st chromosome, in germ cells (sex cells). Some scientists have presented the idea of completely switching off the extra 21st chromosome.

However, in theory, it’s possible to edit germ cells and remove the extra chromosome. But when use CRISPR, it needs to be delivered to every cell. That is again a hurdle.

Moreover, it’s also difficult to know which cells will be trisomy 21. Because research has shown that most of the down syndrome occurs due to random mutation, and maternal age is a factor which increases the chances. While still targeting each cell in the embryo is very time consuming, expensive and nearly impossible.

Alternatively, instead of editing embryo, we can screen for Down’s syndrome embryos via preimplantation genetic diagnosis. Moreover, with the help of in-vitro fertilization, we can maximize the chances for the birth of the healthy fetus.

Currently, preimplantation genetic diagnosis and IVF are better options than using CRISPR.

Video: CRISPR allows scientists to make precise edits to DNA strands, which could lead to treatments for genetic diseases.

CRISPR and Down’s Syndrome: Current Research Done

In 2017, a group of Chinese Researchers reported that CRISPR could be used to eliminate or switch off an extra chromosome. They did so in a mice model with Human 21 chromosome trisomy.

They were able to turn off or delete this entire chromosome by either using a single sgRNA with multiple cleavage sites or using multiple sgRNA, each with a unique cleavage. The study provides hopes for the future, using CRISPR for curing Down’s syndrome.

Another study published by Chinese Scientist shows that CRISPR/cas9 based chromosomal editing efficiency can be increased when used two sgRNA. The idea was to cleave at two points and then with Homology-Directed Repair system, that cleaved part will be taken out. While the remaining will be joined together. Moreover, they also showed that based on literature about 10-200 ng/ul of the Cas9 enzyme would be enough to cleave on the chromosomal level.

They choose two methods that were considered as best for editing chromosomes in mouse models for Down’s syndrome and other for chromosomal abnormalities. First one involves the direct injection into zygotes, which is risky but it needs to be targeted all the infected cells. While other strategy is using embryonic stem cells and then inserting them into the body.

Future Perspectives

CRISPR has such a vast potential to target almost any region of DNA as long as we know the sequence of that region. Moreover, it can also be used to eliminate or switch off an entire chromosome. Meanwhile, the CRISPR technology faced some challenges, particularly its off-target effects. The researchers hoped that in the near future they could overcome these hurdles and use CRISPR as a potential tool treatment of genetic disorders.

Explore More: 11 Diseases CRISPR Technology Could Cure!

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