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Old 04-29-2004, 11:09 PM
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DNA computing takes a diagnostic leap forward

DNA computing holds great promise for use in massively parallel computations. So far, DNA has been used for some complex mathematical problems and even has been used for playing tic-tac-toe. Late in 2001, researchers at the Weizmann Institute in Israel announced the creation of a "programmable DNA computer" that could be used to answer simple yes or no questions, but this week they have upped the ante considerably. In this week's issue of Nature, scientists at the institute have created a DNA computer which offers the means to diagnose and treat certain types of cancer.

In their computer, the state of the current surroundings is determined through several DNA "transitional molecules." These pieces of DNA assess the messenger RNA activity of several genes that are associated with certain types of cancer. The transitional molecules then serve as input to a diagnostic molecule. The diagnostic molecule contains DNA overhangs that are complimentary overhangs for the transition molecules. When the correct transitional molecules pair with their associated overhangs on the diagnostic molecule, the diagnostic molecule is cleaved by a restriction enzyme Fok1. If all the mRNA activity conditions are met, a piece of single stranded DNA (output) is released by the diagnostic molecule. This single stranded DNA is modeled after a known anticancer drug. If the mRNA activity conditions are not met, a different diagnostic molecule releases a piece of single stranded DNA that is suppresses the effect of the anticancer drug.

This model offers specificity for the mRNA activity for distinct types of cancer, and the entire scheme is also quite flexible. Any sufficiently long RNA molecule can act as an indicator, and any piece of single stranded DNA (up to 21 nucleotides) can be released as a "drug." The researchers have also successfully demonstrated their DNA computer under a variety of conditions in a test tube. Unfortunately, the scheme has a long ways to go until it can be used in the treatment of cancer in vivo.

"It is a little early to start thinking about applications," cautions DNA computer expert Lloyd Smith from the University of Wisconsin, Madison. "But it is an important conceptual leap." DNA computers are not new but this is the first in which both input and output are biological, which means it can be hooked up to living systems

As is, the DNA computer would not survive if released into the bloodstream of an individual. The DNA introduced could cause an immune reaction from the individual, and the Fok1 enzyme could create havoc within cells. What is needed is a small delivery module that would encapsulate the entire DNA computer machinery. This module would need to allow different RNA molecules to diffuse in and allow the released drug to diffuse out, all while keeping the guts of the computer inside. While it will be years before this method can be used for fighting disease, it is an ingenious leap that can spur additional research into the field of DNA computing.

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