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Title: Modular protein-oligonucleotide signal exchange

Journal Article · · Nucleic Acids Research
ORCiD logo [1];  [2]
  1. Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Chemical and Biomolecular Engineering; Univ. of Colorado Medicine, Aurora, CO (United States). Dept. of Bioengineering
  2. Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Chemical and Biomolecular Engineering, Dept. of Chemistry, and Dept. of Computer Science

While many methods are available to measure the concentrations of proteins in solution, the development of a method to quantitatively report both increases and decreases in different protein concentrations in real-time using changes in the concentrations of other molecules, such as DNA outputs, has remained a challenge. Here, we present a biomolecular reaction process that reports the concentration of an input protein in situ as the concentration of an output DNA oligonucleotide strand. This method uses DNA oligonucleotide aptamers that bind either to a specific protein selectively or to a complementary DNA oligonucleotide reversibly using toehold-mediated DNA strand-displacement. It is possible to choose the sequence of output strand almost independent of the sensing protein. Using this strategy, we implemented four different exchange processes to report the concentrations of clinically relevant human α-thrombin and vascular endothelial growth factor using changes in concentrations of DNA oligonucleotide outputs. These exchange processes can operate in tandem such that the same or different output signals can indicate changes in concentration of distinct or identical input proteins. The simplicity of our approach suggests a pathway to build devices that can direct diverse output responses in response to changes in concentrations of specific proteins.

Research Organization:
Johns Hopkins Univ., Baltimore, MD (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
SC0010595
OSTI ID:
1630481
Alternate ID(s):
OSTI ID: 1659413; OSTI ID: 1798465
Journal Information:
Nucleic Acids Research, Vol. 48, Issue 12; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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