Wageningen scientists have set the first step towards a cancer treatment that only kills malignant cells. They successfully programmed gene-editing technology CRISPR to recognize tumor DNA and neutralize it.
Cancer cells excel at evading detection, but subtle chemical differences set them apart from healthy cells. Wageningen researchers, together with colleagues in the United States, have now identified a way to exploit this distinction. Using a variant of CRISPR, a modern tool for cutting DNA, they distinguished tumour DNA from healthy DNA and selectively cleaved only the former. The study, published today in Nature, marks an early but promising step towards a cancer therapy that targets and destroys tumour cells with high precision.
The new method relies on methyl groups, small chemical tags on the DNA that switch genes on or off. This so-called DNA methylation, normally ensures that genes needed by a particular cell type are active by switching off unnecessary genes. Methylation patterns in cancer cells vary from those in healthy cells and can act as a molecular âfingerprintâ that helps researchers differentiate malignant cells from healthy ones.
Precision gene editing with ThermoCas9
The team used ThermoCas9, a CRISPR variant they discovered in bacteria several years ago. Like other CRISPR systems, researchers can programme ThermoCas to locate and cut specific sections of DNA within a cell. In laboratory experiments, the researchers introduced this system into human cells grown in culture dishes: healthy cells in one dish and tumour cells in another. They programmed ThermoCas to detect genes that are methylated in healthy cells but unmethylated in tumour cells.
This approach worked: ThermoCas cut DNA in tumour cells while leaving healthy DNA intact. The system thus proved capable of detecting the subtle chemical difference between healthy and tumour cells and acting on it. âThis makes this ThermoCas the first CRISPR-associated enzyme to respond to differences in DNA methylationâ, says John van der Oost, one of the authors of the paper. âIt means we now have a system that we can target specifically towards tumour cells.â
The study represents the first time a CRISPR-based method has relied on methylation to target human cancer cells. âThermoCas9 uses methylation like an address to precisely target cancer cells while leaving healthy cells untouched,â says Hong Li of the Van Andel Institute
 (Michigan, USA). âThe findings could be a game changer.â
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