DNA computers go medical

New automaton promises to diagnose cancer and administer a therapy.

Ten years ago, computer scientist Leonard Adleman surprised the world by demonstrating the first DNA-based computation. While his first calculation was a only a proof of principle - a simple task performed with an inordinate amount of benchwork - it soon became clear that DNA computers might one day become really useful if they could be fully automated and reduced to the scale of the cell. Now Ehud Shapiro’s group at the Weizmann Institute of Science, Israel, claims to have created a DNA automaton that can ’diagnose’ symptoms of cancer and administer a ’therapy’ - at least in vitro. 

In some cancers, including most prominently prostate cancer, the routine diagnosis is already based on molecular signatures rather than anatomical anomalies. Using the gene expression levels that doctors commonly use to recognise this cancer, Shapiro’s group designed a computational DNA molecule that can deal with a series of five yes/no questions in order to establish whether the typical markers of prostate cancer are present or not. Essentially, the molecular computer needs five positive replies ( ie five markers to be present) to be able to release the drug.

The molecular computer is a long DNA hairpin containing the drug molecule (a short strand of DNA that interferes with gene regulation) in its bend. The double-stranded stem of the hairpin contains five ’locks’, each of which can be opened and removed by a molecular recognition event triggered by the presence of the diagnostic messenger RNA in the amounts surpassing a defined threshold. When all five locks have been broken, the drug is released.

The researchers successfully applied this automaton to a test system that recreates the typical molecular signatures of prostate cancer in vitro, then went on to carry out a similar ’treatment’ on a test tube model of small cell lung cancer. Nevertheless, Shapiro remained cautious in his press interviews. ’It may take decades before such a system operating inside the human body becomes reality,’ he said. Apart from the concern of how well the molecular computer would survive in the body, the very process of introducing genetic material into a (possibly healthy) person would need to be considered carefully. Unlike the test tube with the cancer models, the body may contain edited mRNAs or protein factors that bind to the DNA computer in ways that cannot easily be predicted even when the entire genome sequence is cross checked beforehand.

This work takes the non-natural applications of DNA, which have been more like a molecular playground for the past 10 years, back to the real world and to the prospect of real usefulness.

In a similar development from the field of artificial 3D structures built from DNA, Gerald Joyce’s team at The Scripps Research Institute, La Jolla, California, has introduced clonable DNA strands that fold up to form octahedra all by themselves. Bringing together the structural and computational powers of DNA with its natural efficiency to work and replicate on the single molecule level bears immense promise for nanotechnology and medicine.

Michael Gross