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Current Affairs

Protein that helps in precise gene editing

Date: 07 October 2019 Tags: Biotechnology

Issue

Researchers at CSIR-IGIB have discovered a protein variant from a different species of bacteria that can edit the DNA with very high precision.

 

Background

In the currently used tool for gene editing, CRISPR technology, Cas9 protein behaves like a molecular scissors that cuts the DNA at a specific location and inserts a foreign piece of DNA to correct the mutation that causes the disease.

 

Details

  • The commonly used Cas9 protein from Strepotococcus pyogenes bacteria (SpCas9) and its engineered derivative tend to potentially bind to DNA at multiple unintended sites thereby leading to unnecessary alterations in the DNA.

  • The researchers found their new Cas9 protein, which binds and cuts the DNA, was able to correct sickle cell anaemia mutation in patient-derived stem cells.

  • The protein (FnCas9) used by the researchers to edit the DNA is derived from a bacterium — Francisella novicida.

  • The Cas9 protein is supposed to bind to the DNA only when there is a perfect match between the DNA and the protein but  the currently used SpCas9 protein binds and cleaves the DNA at unintended places.

  • The new FnCas9 protein showed negligible binding when there exists more than one mismatch in the target DNA.

  • The FnCas9 protein was found to increase the HDR repair rate fourfold compared to the widely used SpCas9.

Problems associated with old cas9 protein

  • If the Cas9 protein remains bound to DNA at mismatched locations for a long time, there is a possibility that it might cut the DNA at these locations.

  • The Cas9, if bound at multiple unintended sites then the transcription machinery gets stalled and the expression of genes at these locations might be altered.