In vitro selection of non-cross hybridizing oligonucleotides for computation

  • Authors:

  • Hong Bi;Junghuei Chen;Russell Deaton;Max Garzon;Harvey Rubin;David Harlan Wood

  • Affiliations:

  • Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA (E-mail: hongbi@udel.edu;Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA (E-mail: junghuei@udel.edu);Computer Science and Engineering, University of Arkansas, Fayetteville, AR 72701, USA (E-mail: rdeaton@uark.edu);Computer Science, University of Memphis, Memphis, TN 38152-3240, USA (E-mail: mgarzon@memphis.edu);School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA (E-mail: rubinh@mail.med.upenn.edu);Computer and Information Science, University of Delaware, Newark, DE 19716, USA (E-mail: wood@cis.udel.edu)

  • Venue:
  • Natural Computing: an international journal
  • Year:
  • 2003

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Abstract

Since they minimize errors from cross-hybridizations,DNA oligonucleotides that annealas 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-crosshybridizationwas 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 amplifiesmaximally mismatched oligonucleotides overthose that were more closely matched.Experiments confirmed this property of the protocol, and in addition, a reaction temperature window was identified in whichdiscrimination between matched and mismatched might be obtained.The protocol was iterated on a set of random starting material, andthere was evidence that non-crosshybridizing libraries were in factbeing created. These results are a step toward practical manufacture of very large libraries of non-crosshybridizing oligonucleotides in the test tube.