Scientists Develop New Protein Capable of Precisely Controlled Gene Editing

A team of researchers from A*STAR's Genome Institute of Singapore (GIS) and Nanyang Technological University, Singapore (NTU Singapore) has successfully developed a new CRISPR- associated protein that can alter the DNA of living cells with more precision compared to other existing methods.

The new protein, described in a paper published in the journal Nature Chemical Biology, can be controlled by an external chemical input to accurately alter DNA of cells with minimal unintended modifications in other DNA in the cells. Unintended cell modifications are the main problem of the existing CRISPR-Cas1, the gold-standard for DNA altering. By minimizing the unintended modifications, dire consequences could be prevented.

"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 lead author Dr Tan Meng How, Senior Research Scientist of Stem Cell & Regenerative Biology at the GIS, and Assistant Professor at NTU's School of Chemical and Biomedical Engineering, in a press release. "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."

Dubbed as iCas, the new protein could be induced with the help of tamoxifen, a drug commonly used to treat and prevent breast cancer. With the presence of tamoxifen, the protein will be switched on to edit targeted DNA sites. On the other hand, iCas will remain off in the absence of tamoxifen.

In the study, the researchers noted that the faster response time and ability to be turned on and off repeatedly enables gene editing in a precisely-controlled manner. Precision control is very important in the field of gene editing. With the help of iCas, scientists can now engineer cells with new properties or repair diseased cells with mutated DNA, potentially tackling human disease that have very few treatment options.