CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.
CRISPR - Cas9 is the most prominent genome editing technique .
It allows researchers to permanently modify genes in living cells and organisms.
This can be used to correct mutations at precise locations in the human genome to treat genetic causes of diseases.
Correcting the mutation in an embryo ensures that the child is born healthy and the defective gene is not passed on to future generations.
How does it work?
The gene editing tool has two components :
a single-guide RNA (sgRNA) that contains a sequence that can bind to DNA.
the Cas9 enzyme which acts as a molecular scissor that can cleave DNA.
In order to selectively edit a desired sequence in DNA, the sgRNA is designed to find and bind to the target.
The genetic sequence of the sgRNA matches the target sequence of the DNA that has to be edited.
Upon finding its target, the Cas9 enzyme swings into an active form that cuts both strands of the target DNA.
One of the two main DNA-repair pathways in the cell then gets activated to repair the double-stranded breaks.
While one of the repair mechanisms result in changes to the DNA sequence, the other is more suitable for introducingspecific sequences to enable tailored repair.
In theory, the guide RNA will only bind to the target sequence and no other regions of the genome.
But the CRISPR-Cas9 system can also recognise and cleave different regions of the genome than the one that was intended to be edited.
These “off-target” changes are very likely to take place when the gene-editing tool binds to DNA sequences that are very similar to the target one.
Though many studies have only found few unwanted changes suggesting that the tool is probably safe, researchers are working on safer alternatives.
Why is CRISPR- Cas9 system significant?
Normally, if sperm from a father with one mutant copy of the gene is fertilized in vitro with normal eggs, 50% of the embryos would inherit the condition.
However, when the gene-editing tool was used, the probability of inheriting the healthy gene increased from 50 to 72.4%. There was also no off-target snipping of the DNA.
The edited embryos developed similarly to the control embryos indicating that editing does not block development.
Clinical trials are under way in many countries to use this tool for treating cancer.
It was shown in mice that it is possible to shut down HIV-1 replication and even eliminate the virus from infected cells.
In agriculture, a new breed of crops that are gene-edited will become commercially available in a few years.
Given all these, making gene editing possible in human reproductive cells deserves serious considerations in terms of legal, social and ethical consequences.
