Methods and materials for multiplexed collections of functional ligands
Inventors
Jackson, George W. • Batchelor, Robert • Chiu, Alexander S. • Drabek, Rafal • Thirunavukarasu, Deepak • Bruns, Caitlin
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Assignees
Member
Base Pair BiotechnologiesBase Pair Biotechnologies specializes in custom aptamer discovery and development for research, diagnostics, therapeutics, and industrial applications. The company leverages proprietary multiplex selection, advanced bioinformatics, and chemical modification techniques to develop high-affinity and selective nucleic acid aptamers. Base Pair enables affinity reagent development, biosensor design, and molecular detection for a broad range of targets and partners across academia and industry.
Base Pair Biotechnologies specializes in custom aptamer discovery and development for research, diagnostics, therapeutics, and industrial applications. The company leverages proprietary multiplex selection, advanced bioinformatics, and chemical modification techniques to develop high-affinity and selective nucleic acid aptamers. Base Pair enables affinity reagent development, biosensor design, and molecular detection for a broad range of targets and partners across academia and industry.
Publication Number
US-11970785-B2
Publication Date
2024-04-30
Expiration Date
Abstract
This invention relates to methods and materials for multiplexed utilization of collections of functional ligands, particularly to methods and materials for selecting for and/or utilizing particular desirable traits of functional ligands in a multiplexed manner, and more particularly to methods and materials for selecting for and/or utilizing particular structural changes of functional ligands in a multiplexed manner.
Core Innovation
This invention relates to methods and materials for multiplexed utilization of collections of functional ligands, particularly to methods and materials for selecting for and/or utilizing particular desirable traits of functional ligands in a multiplexed manner, and more particularly to methods and materials for selecting for and/or utilizing particular structural changes of functional ligands in a multiplexed manner. In general, functional ligands may be selected for and/or utilized for their ability to bind or complex to particular target molecules, and/or for the manner in which they bind or complex to particular target molecules, such as by exhibiting a detectable structural change.
The background describes that aptamers are nucleic acid ligands whose specificity and characteristics are determined by their secondary and/or tertiary structure and that SELEX typically begins with a very large pool of randomized polynucleotides which is generally narrowed to one aptamer ligand per molecular target. The present invention addresses the need to select for and utilize particular structural changes of functional ligands in a multiplexed manner to enable selection, detection, and use of members of collections based on their structural/conformational changing properties.
Claims Coverage
The claims include one independent claim that recites four main inventive features relating to an arrayed nucleic acid system for detecting binding via hybridization changes.
Substrate with plurality of single-stranded nucleic acid ligands at predetermined addresses
providing a substrate with a plurality of single-stranded nucleic acid ligands located and attached at predetermined addresses on said substrate
Aptamers with an identical hybridization sequence forming hybrids to single-stranded nucleic acid labels
each of said single-stranded nucleic acid ligands being an aptamer binding to a known target molecule with an identical hybridization sequence for each of said single-stranded nucleic acid ligands at one of said predetermined addresses, and forming a hybridization to a single-stranded nucleic acid label, each comprising a complementary hybridization sequence to said hybridization sequence
Incubation of the substrate with a sample potentially containing target molecules
incubating said substrate with a sample which may potentially contain at least one target molecule which binds to at least one of said plurality of single-stranded nucleic acid ligands
Detection of hybridization changes correlated to addresses to indicate binding
determining if any changes in said hybridizations occur after said incubating by performing a detection operation to detect potential changes in said hybridizations between said single-stranded nucleic acid labels and said single-stranded nucleic acid ligands correlated to said addresses; wherein said potential changes in said hybridizations indicate binding of said at least one target molecule to at least one of said plurality of single-stranded nucleic acid ligands when a change in said hybridization occurs after adding said sample and no change in said hybridization after adding said sample indicates no binding of said at least one target molecule to any of said plurality of single-stranded nucleic acid ligands.
The independent claim covers an arrayed nucleic acid system in which aptamer ligands with identical hybridization sequences form hybrids to complementary single-stranded labels at predetermined addresses, the array is incubated with a sample, and hybridization changes are detected and correlated to addresses to indicate presence or absence of target binding.
Stated Advantages
These methods may be utilized to distinguish between structural/conformational switching functional ligands and binding functional ligands which do not undergo such switching behavior.
Structural/conformational switching functional ligands may be more preferable or desirable to use in particular applications where the structural/conformational switching is more easily detected or quantified as opposed to non-switching binding events.
Some switching events may enable or aid in "one step" detection methods.
Documented Applications
Selecting members of a collection for binding activity to particular target molecule(s) which may result in a desired structural change of the binding member(s).
Utilizing a collection of functional ligands to detect and/or quantify the presence or absence of target molecule(s) in a sample and to determine abundance and/or concentration of a target molecule(s) in the sample.
Determining whether members of a collection bind to more than one target molecule or whether binding events are affected by the presence of multiple target molecules (cross-reactivity or multi-target binding).
Use of functional ligands as sensors, therapeutic tools, to regulate cellular processes, and to guide drugs to their specific cellular target(s).
Use of immobilized capture elements in a microarray format and similar spatially organized substrates to detect structure-changing binding events.
Detection and selection examples explicitly described with target molecules lipoarabinomannan (LAM), Tetrakis (hydroxymethyl) phosphonium sulfate (THPS), and bronopol.
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