Why in news
The International Agency for Research on Cancer reported that cancer cases and deaths are increasing globally, with significant risks associated with genetic mutations.
BRCA Genes and Hereditary Cancer
BRCA1 and BRCA2 genes are crucial for DNA repair; mutations in these genes significantly increase the risk of developing breast and ovarian cancers.
Approximately 10% of cancer cases involve inherited mutations, with BRCA mutations found in about 1 in 400 individuals.
In populations such as Ashkenazi Jews, about 1 in 40 individuals carry BRCA mutations, a rate 10 times higher than the general population.
Besides breast and ovarian cancers, BRCA mutations are linked to increased risks of prostate cancer, pancreatic cancer, and some colorectal cancers.
Advances with CRISPR Technology
CRISPR-Cas9 technology allows researchers to create specific mutations in BRCA genes to study cancer development and treatment responses.
Advances include identifying how BRCA mutations affect sensitivity to treatments like PARP inhibitors.
CRISPR gene-editing tool
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a powerful tool used to make precise changes to the DNA of organisms
It uses guide RNA to direct the Cas9 or Cas12 protein to a specific DNA sequence where it makes cuts or modifications.
Widely used in genetic research, medicine, and agriculture to edit genes, improve crops, and potentially treat genetic disorders
But they are too bulky for plant cells to accommodate.
It usually involves the introduction of a new gene, or suppression of an existing gene, through a process described as genetic engineering.
CRISPR technology does not involve the introduction of any new gene from the outside.
CRISPR-Cas9 technology is often described as ‘Genetic Scissors’.
Its mechanism is often compared to the ‘cut-copy-paste’, or ‘find-replace’ functionalities in common computer programmes
A bad stretch in the DNA sequence, which is the cause of disease or disorder, is located, cut, and removed and then replaced with a ‘correct’ sequence.
The tools used to achieve this are biochemical i.e., specific protein and RNA molecules.
The technology replicates a natural defence mechanism in some bacteria that uses a similar method to protect itself from virus attacks.
Mechanism:
The first task is to identify the particular sequence of genes that is the cause of the trouble.
Once that is done, an RNA molecule is programmed to locate this sequence on the DNA strand
After this Cas9 is used to break the DNA strand at specific points, and remove the bad sequence.
A DNA strand, when broken, has a natural tendency to re-attach and heal itself. But if the auto-repair mechanism is allowed to continue, the bad sequence can regrow.
So, scientists intervene during the auto-repair process by supplying the correct sequence of genetic codes, which attaches to the broken DNA strand.
The entire process is programmable, and has remarkable efficiency, though the chances of error are not entirely ruled out.
Limitations
CRISPR-Cas9 system can also recognise and cut parts of the genome other than the intended portion.
Such “off-target” effects are more common when using the SpCas9 enzyme derived from Streptococcus pyogenes bacteria.
Scientists have been able to engineer versions of SpCas9 with higher fidelity but only at the cost of editing efficiency
Recent Findings
Recent studies identified numerous mutations in genes like RAD51C that also increase cancer risk, emphasizing a spectrum of genetic risk.
These findings support tailored prevention strategies and treatments, improving cancer management and early detection.
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