Sunday, May 20, 2007

DNA detection


Picture taken from Hammond, D.M., Manetto, A., Gierlich, J., Azov, V.A., Gramlich, P.M.E., Burley, G.A., Maul, M., Carell, T. Angew. Chem. Int. Ed. 2007, 46, 4184. 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

In my mind, the future of cancer therapy is in the hands of personalized medicine; as the genetic makeup of each patient is different, it only makes sense to utilize customized therapies depending on the mutation affecting the individual. (Just look at the story of Iressa, and how well it works for Asian nonsmoking women with mutations in the EGFR tyrosine kinase domain). While the idea is a great one, personalized therapy is not a reality yet. Currently treatment options are too limited and often unspecific; methods to detect various disease markers are lacking. Personalized medicine depends upon the detection of minute amounts of DNA as well as isolation of particular genes from biological samples of interest, and the Carell group has developed a method to help with this.

Typically PCR is used for standard DNA amplification, although newer, more sophisticated techniques have allowed for detection of DNA down to the zeptomolar 10-21 level. (I'd never even heard of that one, my super-geeky husband had to fill me in). Unfortunately, such methods require the use of expensive/complex technology, so Carell and coworkers have developed a simple method of DNA detection based on standard black and white photography techniques. First, a pinacyanol dye was modified to contain an azide functionality, and several alkyne-containing oligodeoxyribonucleotides (ODNs) were synthesized. After a copper catalyzed Huisgen cycloaddition, various concentrations of modified ODNs were spotted down on commercial photopaper, irradiated, and developed according to known methods (standard photographic darkroom setup). This simple procedure allows for the detection of ~300 attomoles (10-18) of DNA!

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