Singapore scientists develop DNA-altering technology to tackle diseases

Researchers in Singapore have developed a new protein that can alter DNA in living cells with much higher precision than current methods. 

This new protein, named iCas, can be easily controlled by an external chemical input and thus solves some of the problems with CRISPR-Cas, the existing gold-standard for DNA altering. For example, existing Cas enzymes may sometimes alter places in the DNA that result in dire consequences. With iCas, users now have the ability to control enzyme activity and thus minimize unintended DNA modifications in the cell.

"DNA is like an instruction manual that tells living cells how to behave, so if we can rewrite the instructions in this manual, we will be able to gain control over what the cells are supposed to do," explained Dr Tan. "Our engineered iCas protein is like a light switch that can be readily turned on and off as desired. It also outperforms other existing methods in terms of response time and reliability."

To ensure that DNA is precisely altered, which is required in many biomedical and biotechnological applications, the activity of the Cas protein must be tightly regulated.

The chemical that switches the iCas protein on or off is tamoxifen, a drug commonly used to treat and prevent breast cancer. In its absence, iCas is switched off with no changes made to the DNA. When switched on with tamoxifen, iCas will then edit the target DNA site.

In the study, iCas was found to outperform other chemical-inducible CRISPR-Cas technologies, with a much faster response time and an ability to be switched on and off repeatedly.