Subhiksha D

Genomeden Writing Internship Participant

MSc. Human Genetics and Molecular Biology,

Department of Human Genetics and Molecular Biology,

Bharathiar University,

Coimbatore.,Tamil Nadu – 641 046

From a lawn mower to an exquisite Italian pasta, everything has its own guide manuals to marshal it. Likewise for living organisms, these manuals have been inbuilt in the form of the ‘genome’. Let’s think of the genome as one’s manual for all functions in living organisms including traits like eye color, height, etc., written in a cryptic code of four letters – namely A, T, G, and C, known as ‘nitrogenous bases’. And this book has 3 billion of these bases as different DNA sequence orders for each individual, making each one of us unique, yet similar as species. These letters as a group three in any random order form a codon, or in other words, forming a “word” that makes sense. Each codon codes for an amino acid that in turn contributes to making protein, executioners of traits and functions.

Imagine accidentally misspelling a letter in it; Does it matter? Can it be overlooked?

It’s complicated, at least until knowing behind the scenes. 

Like how one small move may or may not tumble a jenga tower, the error in the DNA sequence (made of A, T, G and C) may result in various genetic disorders or rather change nothing at all.  

When just a misspelled letter could have the possibility of resulting in fatal disorders, then is there a possibility to correct it? Like sneaking in an eraser to cheat our inherent code, maybe? It does, with a technology called ‘genome editing’. Just like tweaking our pictures for a better social media post, this technology aids in making base specific alterations.This  technology aims in improving treatment options for genetic disorders like sickle cell anemia, that are caused due to single-gene defects.

Genome editing technology was introduced in the 1900s, where they worked on exploiting our cells’ inbuilt DNA repair mechanism that stitches together any breaks in the DNA. It employs specialized enzyme complexes that act like scissors to cut the DNA sequence specific programmed site. Some of the earlier established technologies are meganucleases, zinc finger nucleases (ZNF) and transcription activation – like effector nucleases  (TALENs). Each of these technologies have replaced the short-comings of its preceding technology and yet lacked efficiency and precision.

But no worries! Reference from nature has come to rescue. A Nobel prize bagging finding in 2012 by J. Doudna and E. Charpentier, which led to the development of a new gene editing tool, inspired from the adaptive immune response of bacterial species against viruses.  The bacterial version of this technology is built-in; it basically snips off bits of DNA of its pathogenic invader and incorporates these into their genome (Just like collecting souvenirs, in immunological terms!). It aids in damaging any genetically similar virus in future. The region of collection of pathogenic snippets is called – clustered regularly interspaced short palindromic repeats, i.e, CRISPR in short. 

The spin-off version of this tool, “CRISPR-cas9” consists of a dual complex – a ‘cas9 enzyme’, that acts as molecular scissors to cut DNA and a guide RNA that acts as GPS to locate this enzyme to a specific target sequence to make the cut. CRISPR – cas9 complex can be used to delete or insert or modify a base or even to inactivate genes by DNA breaks. It has immense potential in research as well as a clinical tool and much more. 

But with great potential tags a greater risk and restrictions associated. While this technology is still in its infancy for human usage, there also exists an illegal case of a chinese scientist He Jiankui performing CRISPR-cas9 based editing on human embryos in 2018, which was not approved yet. So I’ll leave you here to ponder on – ‘is all the stringent regulation holding back the applicational development of gene editing techniques like CRISPR or is it just preventing the misuse of it?’


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