Sequence-Specific Detection of Unlabeled Nucleic Acid Biomarkers Using a “One-Pot” 3D Molecular SensorCitation formats

  • External authors:
  • Sameen Yousaf
  • Patrick J.s. King
  • David John Clarke
  • Linda T. Trivoluzzi

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Sequence-Specific Detection of Unlabeled Nucleic Acid Biomarkers Using a “One-Pot” 3D Molecular Sensor. / Yousaf, Sameen; King, Patrick J.s.; Miller, Aline F.; Saiani, Alberto; Clarke, David John; Trivoluzzi, Linda T.; Aojula, Harmesh Singh; Bichenkova, Elena V.

In: Analytical Chemistry, 06.08.2019.

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@article{a1ef826f6cd44d118370fa1bbcdad042,
title = "Sequence-Specific Detection of Unlabeled Nucleic Acid Biomarkers Using a “One-Pot” 3D Molecular Sensor",
abstract = "DNA and RNA biomarkers have not progressed beyond the automated specialized clinic due to failure in the reproducibility necessary to standardize robust and rapid nucleic acid detection at the point of care, where health outcomes can be most improved by early-stage diagnosis and precise monitoring of therapy and disease prognosis. We demonstrate here a new analytical platform to meet this challenge using functional 3D hydrogels engineered from peptide and oligonucleotide build-ing blocks to provide sequence-specific, PCR-free fluorescent detection of un-labelled nucleic acid sequences. We discrimi-nated at picomolar detection limits (<7 pM) ‘perfect-match’ from mismatched sequences, down to a single nucleotide muta-tion, buried within longer lengths of target. Detailed characterisation by NMR, TEM, mass spectrometry and rheology pro-vided the structural understanding to design these hybrid peptide-oligonucleotide biomaterials with the desired sequence sen-sitivity and detection limit. We discuss the generic design, which is based on a highly-predictable secondary structure of the oligonucleotide components, as a platform to detect genetic abnormalities and to screen for pathogenic conditions at the level of both DNA (e.g. SNPs) and RNA (messenger, micro and viral genomic RNA).",
author = "Sameen Yousaf and King, {Patrick J.s.} and Miller, {Aline F.} and Alberto Saiani and Clarke, {David John} and Trivoluzzi, {Linda T.} and Aojula, {Harmesh Singh} and Bichenkova, {Elena V.}",
year = "2019",
month = "8",
day = "6",
doi = "10.1021/acs.analchem.9b01841",
language = "English",
journal = "Analytical Chemistry",
issn = "0003-2700",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Sequence-Specific Detection of Unlabeled Nucleic Acid Biomarkers Using a “One-Pot” 3D Molecular Sensor

AU - Yousaf, Sameen

AU - King, Patrick J.s.

AU - Miller, Aline F.

AU - Saiani, Alberto

AU - Clarke, David John

AU - Trivoluzzi, Linda T.

AU - Aojula, Harmesh Singh

AU - Bichenkova, Elena V.

PY - 2019/8/6

Y1 - 2019/8/6

N2 - DNA and RNA biomarkers have not progressed beyond the automated specialized clinic due to failure in the reproducibility necessary to standardize robust and rapid nucleic acid detection at the point of care, where health outcomes can be most improved by early-stage diagnosis and precise monitoring of therapy and disease prognosis. We demonstrate here a new analytical platform to meet this challenge using functional 3D hydrogels engineered from peptide and oligonucleotide build-ing blocks to provide sequence-specific, PCR-free fluorescent detection of un-labelled nucleic acid sequences. We discrimi-nated at picomolar detection limits (<7 pM) ‘perfect-match’ from mismatched sequences, down to a single nucleotide muta-tion, buried within longer lengths of target. Detailed characterisation by NMR, TEM, mass spectrometry and rheology pro-vided the structural understanding to design these hybrid peptide-oligonucleotide biomaterials with the desired sequence sen-sitivity and detection limit. We discuss the generic design, which is based on a highly-predictable secondary structure of the oligonucleotide components, as a platform to detect genetic abnormalities and to screen for pathogenic conditions at the level of both DNA (e.g. SNPs) and RNA (messenger, micro and viral genomic RNA).

AB - DNA and RNA biomarkers have not progressed beyond the automated specialized clinic due to failure in the reproducibility necessary to standardize robust and rapid nucleic acid detection at the point of care, where health outcomes can be most improved by early-stage diagnosis and precise monitoring of therapy and disease prognosis. We demonstrate here a new analytical platform to meet this challenge using functional 3D hydrogels engineered from peptide and oligonucleotide build-ing blocks to provide sequence-specific, PCR-free fluorescent detection of un-labelled nucleic acid sequences. We discrimi-nated at picomolar detection limits (<7 pM) ‘perfect-match’ from mismatched sequences, down to a single nucleotide muta-tion, buried within longer lengths of target. Detailed characterisation by NMR, TEM, mass spectrometry and rheology pro-vided the structural understanding to design these hybrid peptide-oligonucleotide biomaterials with the desired sequence sen-sitivity and detection limit. We discuss the generic design, which is based on a highly-predictable secondary structure of the oligonucleotide components, as a platform to detect genetic abnormalities and to screen for pathogenic conditions at the level of both DNA (e.g. SNPs) and RNA (messenger, micro and viral genomic RNA).

U2 - 10.1021/acs.analchem.9b01841

DO - 10.1021/acs.analchem.9b01841

M3 - Article

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

ER -