SEP 02, 2020 10:30 AM SGT

Connecting the dots between personalized and precision medicines



The general focus of my lab is to characterize at the molecular level, genome editing proteins derived from the bacterial CRISPR-Cas system and apply them for reversing disease causing mutations. Using biophysical tools, we dissect the mechanism of action of Cas9 proteins with respect to nucleic acid interrogation and use this knowledge to design editors with high gene targeting specificity. We combine biochemical tools for producing recombinant Cas9 proteins, induced pluripotent stem cell (iPSC) technology for studying their efficacy in patient cells and single molecule experiments for evaluating their targeting specificity. Based on this broad theme, there are two key areas where I carry out research on:

1) We have extensively characterised a TypeII Cas9 from Francisella novicida (FnCas9) and demonstrated its ability in genome editing of the sickle cell anemia mutation in patient derived iPSCs and HSCs. FnCas9 is highly specific in target interrogation and produces negligibe background insertions/deletions in patient Hematopoietic stem cells. Currently we are working towards completing pre-clinical studies on FnCas9

2) We have repurposed the high specificity of FnCas9 towards a Point of Care diagnostic assay for detecting nucleotide variants in a target. This can perform with minimum equipment and technical know-how and is being currently deployed for rapid and accurate diagnosis of COVID- 19 positive cases. By tying up with industries, we are scaling up the production of assay components to enable testing on a large scale during the ongoing pandemic.

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