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Universal translators for nucleic acid diagnosis

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Overview

related to degree

  • Frezza, Brian, Ph.D. in Chemical Biology, Scripps Research 2005 - 2010

authors

  • Picuri, J. M.
  • Ghadiri, M. Reza
  • Frezza, Brian

publication date

  • 2009

journal

  • Journal of the American Chemical Society  Journal

abstract

  • Defined broadly, molecular translators are constructs that can convert any designated molecular input into a unique output molecule. In particular, the development of universal nucleic acid translators would be of significant practical value in view of the expanding biomedical importance of gene diagnostics. Currently, diagnostic assays for nucleic acids must be individually developed and optimized for each new sequence because inputs for one assay are sequence-specific and are therefore incompatible with any other assay designed for the detection of a different nucleic acid. However, if a desired nucleic acid sequence could be translated in vitro into a predetermined nucleic acid output for which there is already a known diagnostic assay, then that single assay could be easily adapted to detect nearly any strand. Here we investigate PCR-independent isothermal molecular translation strategies that function without the need for post-translation purification and can be implemented with commercially available components. Translation yields up to 96% are obtained in 5 min at room temperature with minimal background reaction (<1%) and with discrimination of single nucleotide polymorphisms in the input sequence. Furthermore, we apply these translators to adapt a high-gain HIV diagnostic system for high-throughput detection of hepatitis C, avian influenza (H5N1), and smallpox without making changes to the underlying assay. Finally, we show the feasibility of translating small-molecule interactions into nucleic acid outputs by demonstrating the utility of a DNA aptamer for translating adenosine into a readily detectable output DNA sequence. Additionally, equilibrium expressions are described in order to facilitate rational engineering of aptameric translators for label-free detection of any molecule that an aptamer can recognize.

subject areas

  • Adenosine
  • Animals
  • Aptamers, Nucleotide
  • Base Sequence
  • Birds
  • DNA
  • Hepatitis C
  • Humans
  • Influenza A Virus, H5N1 Subtype
  • Influenza in Birds
  • Nucleic Acid Amplification Techniques
  • Polymorphism, Single Nucleotide
  • RNA, Viral
  • Smallpox
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Identity

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja902490x

PubMed ID

  • 19566101
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Additional Document Info

start page

  • 9368

end page

  • 9377

volume

  • 131

issue

  • 26

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