DNA bot targets cancer

By Kimberly Patch, Technology Research News

Researchers from the Weizmann Institute in Israel have constructed a molecular-size computer that is programmed to find signs of cancer cells, and when they are present, dispense DNA molecules designed to eradicate those cells.

The researchers' computer is a proof-of-concept that works only in a test tube, but the device is meant to eventually work in the human body. The prototype shows that "autonomous, molecular-scale systems are able to perform such complex tasks as disease diagnosis and treatment," said Yaakov Benenson, a researcher at the Weizmann Institute.

The computer is small enough that one trillion of them fit in a drop of water. It is made from strands of DNA and operates in liquid. It analyzes the messenger RNA molecules in its environment, and when it finds a balance of RNA levels that indicate a type of cancer it is programmed to recognize, it releases DNA molecules designed to cause cancer cells to self-destruct.

DNA consists of four types of bases -- adenine, cytosine, guanine and thymine -- connected to a sugar-phosphate backbone. The familiar double helix of biological DNA consists of a double strand with connected base pairs. Messenger RNA is a carbon copy of portions of the DNA stored in the nucleus of the cell, and indicates that those portions of the DNA are active.

The molecular computer consists of three modules: input, computation and output.

The input module consists of single strands of DNA that contain stretches of bases that pair up with and so identify certain stretches of messenger RNA. The computation module processes a series of input modules to determine whether the balance of certain types of messenger RNA indicates the presence of cancer cells. The output module administers a drug in the form of another DNA strand when cancer cells are indicated.

The researchers' prototype includes a second type of DNA computer that is programmed to release a DNA strand that inhibits the first computer's drug molecule if cancer cells are not present. Both DNA computers must register the presence of cancer cells for the cancer-fighting DNA strand to be administered.

The researchers' previous work and that of other researchers showed that DNA can be made to perform computations using DNA's ability to match up sequences of base pairs, and enzymes, which can be used to snip strands.

The researchers recently developed a DNA computer that operates without human intervention. They modified the autonomous computer to make the cancer-detecting computer. "We took our existing molecular computer and [changed] its program [to respond] to abnormal messenger RNA labels and/or mutations," he said. "Our computation result depends on these levels, which may indicate a disease."

In their proof-of-concept experiments, the researchers mixed DNA computers programmed to identify prostate cancer in a test tube with prostate cancer cells. The computers were able to identify the cells and release DNA strands designed to eradicate the cells. The researchers programmed a second set of DNA computers to identify a certain form of lung cancer cells, and the computers successfully identified those as well.

The method has the potential to detect multiple disease conditions at once, said Benenson. This "makes the diagnosis very selective," he said.

The key to the method is that the tiny computer is made from a material that is intrinsically compatible with living beings, said Benenson. "In situ detection and analysis of molecular signals in living organisms is impossible with electronic computers due to the insurmountable incompatibility of the materials involved," he said.

The next step is to see if practical applications like real diagnosis and cure are possible using the DNA computers, said Benenson. Even though the materials are biologically compatible, the device itself "will require major modifications to be made compatible with living systems," he said.

The first working smart drugs are likely to sense just a single disease indicator and may become available within the next three to four years. More elaborate smart drugs like the researchers' molecular-scale computer could take 10 years to reach clinical trials, said Benenson.

Benenson's research colleagues were Binyamin Gil, Uri Ben-Dor, Rivka Adar and Ehud Shapiro. The work appeared in the April 29, 2004 issue of Nature. The research was funded by the Israeli Science Foundation, the Moross Cancer Institute and the Minerva Foundation.

Timeline:   3-4 years, 10 years
Funding:   Government; Private
TRN Categories:  Biological, Chemical, DNA and Molecular Computing; Biotechnology
Story Type:   News
Related Elements:  Technical paper, "An Autonomous Molecular Computer for Logical Control of Gene Expression," Nature, April 29, 2004


May 5/12, 2004

Page One

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