Functional ligands to LL37
Inventors
Jackson, George W. • Batchelor, Robert • Nguyen, Truong • SINGER, Victoria • Lee, Garam • Drabek, Rafal
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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-10927381-B2
Publication Date
2021-02-23
Expiration Date
Abstract
The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, such as molecules used proteins or peptides, such as LL37.
Core Innovation
The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, more particularly to functional ligands with binding affinity to molecules such as proteins or peptides, such as LL37.
Aptamers, which are nucleic acid ligands capable of binding to molecular targets, have recently attracted increased attention for their potential application in many areas of biology and biotechnology. SELEX typically begins with a very large pool of randomized polynucleotides which is generally narrowed to one aptamer ligand per molecular target. Recent research has highlighted the overexpression of a 37-amino acid human antimicrobial peptide named LL37 in the pathogenesis of psoriasis, and independently implicated LL37 in rosacea, with LL37-DNA complexes triggering plasmacytoid dendritic cells to produce IFN-α and initiating local activation of autoimmune T-cells that may lead to the development of psoriatic lesions.
Claims Coverage
Two inventive features are identified from the independent claims.
Non-naturally occurring nucleic acid ligands to LL37
An artificial ligand binding to LL37 peptide consisting essentially of a non-naturally occurring nucleic acid sequence having the sequence selected from the group consisting of SEQ IDs 14-18 and 45-49.
Artificial ligand comprising sequence with 100% identity to specified SEQ IDs
An artificial ligand binding to LL37 peptide comprising a non-naturally occurring nucleic acid sequence having 100% sequence identity to a sequence selected from the group consisting of SEQ IDs 14-18 and 45-49.
The independent claims cover artificial ligands to LL37 defined by specific non-naturally occurring nucleic acid sequences (SEQ IDs 14-18 and 45-49) and an embodiment requiring 100% sequence identity to those sequences.
Stated Advantages
High capacity, multiplexed identification procedures may save time, expense, and physical space for the process over single target identification processes.
The method may be utilized to identify and/or eliminate biomolecules that bind or have a tendency to bind to multiple targets.
Marking or tagging bound library members preserves association of a given member with a particular target and is desirable for resolving multiple binders to a single target.
Functional ligands to LL37 may be utilized to aid in inhibiting the action of LL37 in inflammation and may be utilized in therapeutics to treat psoriasis, rosacea and/or other similar conditions.
Functional ligands to LL37 may be used for detection or quantification of such molecules in biological samples and may be utilized to purify the target molecules from a mixture.
Documented Applications
Generating numerous different functional nucleic acids against multiple target molecules simultaneously via multiplexed selection and tagging approaches.
Therapeutic use of functional ligands to LL37 to aid in inhibiting the action of LL37 in inflammation and to treat psoriasis, rosacea and/or other similar conditions, including topical, intravenous or other application routes.
Detection or quantification of LL37 or similar molecules in biological samples using modalities such as fluorescence assays, electrochemical sensors, gold nanoparticle assays, enzyme linked aptamer sorbent assays (ELASA), pull down assays (immunoprecipitation), microplate/well assays, and lateral flow assays.
Purification of target molecules such as LL37 from a mixture using functional ligands.
Use of aptamers as molecular beacons (aptabeacons) that fluoresce or otherwise produce a detectable signal upon binding their target.
Application of multiplexed target arrays and histology sections as target sets for generating affinity binding nucleic acids.
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