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'Nanocircles' act as Trojan horse to shut down disease-causing genes, study finds

Stanford scientists have synthesized a molecule of DNA that is capable of shutting off specific genes in living bacteria. Dubbed the nanocircle, the new nanometer-size molecule might one day give researchers the ability to target harmful genes that cause cancer and other diseases in humans.

In the long range, we hope that nanocircles could be used for genetic therapy in people, said Eric T. Kool, a professor of chemistry at Stanford who led the nanocircle study.

The results were published in the Jan. 8 issue of the Proceedings of the National Academy of Sciences (PNAS) in a paper co-authored by Kool, former postdoctoral fellow Tatsuo Ohmichi and graduate student Angle Maki.

Rolling circles

Kool helped pioneer nanocircle technology in 1991 while at the University of Rochester, where he synthesized the first circular DNA molecules capable of replicating themselves in a test tube when combined with special DNA-copying enzymes and other chemicals.

The technique known as rolling circle amplification is now one of the hottest fields in biotechnology, because it offers the potential to produce and detect more copies of a specific DNA sequence faster and cheaper than other methods.

What is new about the PNAS study is that, for the first time, we used a nanocircle in a living cell the bacterium E. coli, Kool noted.

He and his colleagues wanted to see if a synthetic molecule of circular DNA could target a specific gene in E.coli. To do that, they needed to design a DNA nanocircle that could duplicate large numbers of ribozymes enzymes found in all living cells that are capable of altering the function of individual genes in the organisms DNA. Ribozymes are made of RNA protein-producing molecules manufactured by genes.

Ribozymes are biologically active, Kool said. They can inhibit or shut down a gene by destroying its RNA.

In nature, ribozymes are assembled by DNA
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Contact: Mark Shwartz
mshwartz@stanford.edu
650-723-9296
Stanford University
24-Jan-2002


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