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The polymerase chain reaction (PCR) provides a way to quantitate small amounts of DNA. Now, Ulf Landegren and his colleagues at Uppsala University, in Sweden, have devised a way to harness PCR for sensitive quantitation of proteins [Nat. Biotechnol., 20, 473 (2002)]. Their method, called proximity ligation, is based on two DNA aptamers binding to the target protein. The aptamers have extensions attached to them. When both aptamers bind to the target protein, the extensions come close enough to one another that they both can hybridize to a connector oligonucleotide, be joined by DNA ligation, and be amplified by PCR. The amplified product identifies and quantifies the protein present in the sample. Landegren and colleagues demonstrate the method by detecting 4 3 10–20 mol of the homodimer of the platelet-derived growth factor B-chain. The detection is 1,000-fold more sensitive than an immunoassay for the same protein.







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