22 June 2007

DNA "Computer" Works Inside Living Cells, Suggests Possibilities

Although DNA computers have been made that can play simple games like tic-tac-toe, programming DNA computers to work inside living cells is much more interesting.
The goal is to inject human cells with DNA that can determine whether a cell is cancerous or otherwise diseased, based solely on the mix of molecules inside the cell. Sensing disease, the DNA might trigger a pinpoint dose of treatment in response. That technology, however, is a long way off. For now, researchers are testing different ways of turning DNA into versatile computers that can detect certain combinations of molecules and respond by producing other molecules.

...RNAi is something that cells do naturally. Cells produce what are known as short interfering RNA (siRNA) molecules, which recognize corresponding DNA sequences in genes and cause them to shut down.

Benenson and colleagues engineered a target gene to be sensitive to several different siRNAs of their own design. In the simplest case, they introduced a single siRNA molecule to switch off a target gene that encoded a fluorescent protein. In more complex cases, a pair of siRNAs or either of two siRNAs switched off another target gene, which in turn switched off a gene for a fluorescent protein. To make sure the system worked as intended, the researchers based their siRNAs on those of other species, they report in a paper published online today by Nature Biotechnology.

In principle, the RNAi technique can reach great heights of complexity, Benenson says, by making genes sensitive to more and more siRNAs in various combinations. "The scalability is very important, because eventually you want to make complex decisions," he says.

He says the next step is figuring out how to make the molecules inside a cell—such as those that are overproduced in cancer—trigger the production of siRNAs.

This is a very simple approach to DNA "computing", but for all its conceptual simplicity it suggests possibilities that are much more complex. It is best to go very slowly and carefully. The type of control of gene expression hinted at here is not only promising as a cure for cancers, it is threatening.

This type of research appears ideal for a synthetic biological organism. At this time synthetic biologists are attempting to design the simplest possible cells, from other species, by including the smallest possible gene set for viability. Presumably, as the synth biologists master the simpler life forms, they will attempt to create more complex organisms.

Synthetic organisms could potentially become ideal biological models for studying various human diseases. Eventually, synthetic organisms and biological systems could replace most animal models--eliminating much of the need for animal research and testing.

This is yet another research field that bears close watching.

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