Indian scientists build breakthrough gene-editor, aim for patent Premium

Enhanced genome-editing system developed by CSIR-IGIB scientists offers precise DNA modification with improved efficiency.

Scientists from the CSIR-Institute of Genomics and Integrative Biology, New Delhi, have developed an enhanced genome-editing system that can modify DNA more precisely and more efficiently than existing CRISPR-based technologies.

CRISPR occurs naturally in some bacteria, as a part of their immune system that limits infections by recognising and destroying viral DNA. In Nobel-prize winning work, scientists repurposed this bacterial defence mechanism to develop a novel approach for editing the genomes of higher-order organisms.

Today, using CRISPR-Cas9, researchers can add, remove or alter specific DNA sequences in the genome of animals. This system has been used in various fields, including in agriculture — to improve the nutritional value of plants and increase the yield — and in healthcare to diagnose several diseases and treat genetic disorders.

The CRISPR-Cas9 gene editing tool uses a guide-RNA (gRNA) designed to find and bind to a specific part of the target genome. The gRNA directs an enzyme, Cas9, to the target site, which is followed by a short DNA sequence called protospacer adjacent motif (PAM). Cas9 recognises and binds to the PAM sequence, and acts as a molecular scissor that snips some damaged DNA. This automatically triggers the cell’s DNA repair system, which repairs the snipped part to insert the correct DNA sequence.

But the 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.

To overcome these issues, researchers are exploring Cas9 enzymes from Francisella novicida bacteria. While this Cas9, called FnCas9, is highly precise, it has a low efficiency as well.

To enhance it without compromising its specificity, researchers led by Debojyoti Chakraborty at CSIR-IGIB modified and engineered new versions of FnCas9.