In vitro selection of non-crosshybridizing oligonucleotides for computation


Since they minimize errors from cross-hybridizations, DNA oligonucleotides that anneal as designed are beneficial to DNA computing. By in vitro selection, huge libraries of non-crosshybridizing oligonucleotides might be evolved in the test tube. As a first step, a fitness function corresponding to non-crosshybridization was based upon the duplex stability of randomly matched oligonucleotides. By melting pairs that have a low thermal stability, a protocol based on DNA polymerization selectively amplifies maximally mismatched oligonucleotides over those that were more closely matched. Experiments confirmed this property of the protocol, and in addition, a reaction temperature window was identified in which discrimination between matched and mismatched might be obtained. The protocol was iterated on a set of random starting material, and there was evidence that non-crosshybridizing libraries were in fact being created. These results are a step toward practical manufacture of very large libraries of non-crosshybridizing oligonucleotides in the test tube. © 2003 Kluwer Academic Publishers.

Publication Title

Natural Computing