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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



Engineered fingers spot mistakes in DNA


17 November 2006

Exposing errors in the DNA hidden deep inside our cells should help doctors diagnose certain diseases earlier and more accurately, say US scientists. 

Finding mistakes in DNA can help us detect certain diseases, for example, cancer. In the past, researchers would have to pull the two strands of the DNA double helix apart to detect these errors. Now, scientists can use a method called sequenced-enabled reassembly, or Seer, to detect errors in the DNA double helix directly. 

Zinc finger proteins can be used to detect mistakes in DNA.

Zinc finger proteins can be used to detect mistakes in DNA.

David Segal of the University of California, Davis, helped develop Seer along with Indraneel Ghosh of the University of Arizona, Tucson. The method uses proteins that bind to DNA, called zinc fingers, to scan the DNA within a living cell. When the proteins detect a particular sequence they produce a fluorescent signal. 

"The goal is a sensitive and specific test that can be performed easily in a doctor's office."
There is a need for affordable, less complex methods for the widespread screening of cancers and genetic diseases, said Segal. These methods will help to detect genetic information within living cells, an environment where DNA is double-stranded and experimental manipulation is limited, Segal explained. 'The goal is a sensitive and specific test that can be performed easily in a doctor's office and return an answer quickly,' he said.

"In the future, cells marked with disease-causing DNA, such as HIV-1 DNA, can be selectively eliminated."
Seer's strength lies beyond that of just detection, said Carlos Barbas of the Scripps Research Institute, La Jolla, US, a leader in the field of engineered zinc fingers. He suggests that the Seer method promises to be a powerful approach to disease treatment. For example, it could be used to target cancer cells by switching-on enzymes that convert drug precursors, called prodrugs, into active cytotoxic compounds. 'In the future, cells marked with disease-causing DNA, such as HIV-1 DNA, can be selectively eliminated using the Seer approach and an appropriate enzyme/prodrug system,' said Barbas.

Sarah Corcoran

References

I Ghosh, CI Stains, AT Ooi and DJ Segal, Mol. BioSyst., 2006, 2, 551
DOI: 10.1039/B611169f