Why in the news?

• For about a decade, researchers have used the CRISPR technology for genome editing. However, there are some challenges in the use of CRISPR.
• The first challenge is that the phenotypic, or observable, effects caused by unexpected CRISPR dynamics are not quantitatively monitored.
• A second challenge is that the CRISPR technology generally depends on basic genomic data, including the reference genome. The reference genome is like a template that provides researchers with general information on the genome. Unexpected sequence editing with mismatches can occur. These off-target sites are always unexpected. 
• The DANGER analysis overcomes these challenges and allows researchers to perform safer on- and off-target assessments without a reference genome.
• The discovery holds the potential for applications in medicine, agriculture, and biological research.
  
  

About DANGER (Deleterious and ANticipatable Guides Evaluated by RNA-Sequencing):

• DANGER analysis is a new software tool that makes genome editing safer by overcoming limitations in current CRISPR technology.
• Unlike traditional methods that rely on a reference genome, DANGER works by conducting risk-averse on- and off-target assessments using RNA-sequencing data.
• It evaluates phenotypic effects based on gene expression changes caused by deleterious off-target sites.
• The software quantifies the phenotypic risk at the gene ontology level without the need for a reference genome.
• The tool successfully evaluated the phenotypic effects of gene editing in human cells and zebrafish brains.
• It can be performed on various organisms, personal human genomes, and atypical genomes created by diseases and viruses.
• The open-source nature of the software allows for its adaptation to different genome editing systems beyond CRISPR-Cas9. 

What is genome editing?

• It is a method that lets scientists change the DNA of many organisms, including plants, bacteria, and animals.
• Editing DNA can lead to changes in physical traits, like eye colour, and disease risk.
• Scientists use different technologies to do this.
• These technologies act like scissors, cutting the DNA at a specific spot. Then scientists can remove, add, or replace the DNA where it was cut.

Key Facts about CRISPR-Cas9:

• CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats, which is a reference to the clustered and repetitive sequences of DNA found in bacteria, whose natural mechanism to fight some viral diseases is replicated in this gene-editing tool.
• 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. And the tools used to achieve this are not mechanical, but biochemical — 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.