Functional ligands to lipoarabinomannan

Inventors

Jackson, George W.Batchelor, RobertDrabek, RafalBruns, Caitlin

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Assignees

Base Pair Biotechnologies Inc

Member
Base Pair Biotechnologies
Base Pair Biotechnologies

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-10941444-B2

Publication Date

2021-03-09

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 lipoarabinomannan (LAM).

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 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 lipoarabinomannan (LAM).

The background identifies lipoarabinomannan (LAM) as a lipoglycan and major virulence factor in the bacteria genus Mycobacterium, such as Mycobacterium tuberculosis, which serves as a modulin with immunoregulatory and anti-inflammatory effects allowing the bacterium to maintain survival in the human reservoir by undermining host resistance and acquired immune responses. Functional ligands to LAM are described as potentially useful for detection, quantification, and other diagnostic applications, such as detecting tuberculosis infection in a patient.

Claims Coverage

The claim set includes two independent claims and four main inventive features identified from those claims.

Artificial ligand binding to lipoarabinomannan (LAM)

An artificial ligand that binds to lipoarabinomannan (LAM) as recited in the claims.

Non-naturally occurring nucleic acid under 40 nucleotides with >75% identity to specified SEQ ID Nos.

A non-naturally occurring nucleic acid sequence under 40 nucleotides in length having substantial homology and greater than 75% identity to a sequence selected from SEQ ID Nos. 5, 7, 8, 14, 19, 23, 34, 54 and 61.

Non-naturally occurring nucleic acid with 100% identity to specified SEQ ID Nos.

A non-naturally occurring nucleic acid sequence having 100% sequence identity to a sequence selected from SEQ ID Nos. 3, 5, 7, 8, 14, 19, 23, 34, 54 and 61.

Appended priming sequences (SEQ ID Nos. 70-71)

The non-naturally occurring nucleic acid sequence may be appended with a 5′-sequence, a 3′-sequence, or both, selected from SEQ ID Nos. 70-71, as recited in the claims.

The independent claims collectively cover artificial ligands that bind LAM comprising defined non-naturally occurring nucleic acid sequences of specified sequence identity ranges to listed SEQ ID Nos., and embodiments including appended 5′ and/or 3′ sequences from SEQ ID Nos. 70-71.

Stated Advantages

High capacity, multiplexed identification procedures may save time, expense, and physical space compared to single target identification processes.

The multiplex method may be utilized to identify and/or eliminate biomolecules that bind or have a tendency to bind to multiple targets.

Functional ligands to LAM may be utilized for detection, quantification, and other diagnostic applications, including detecting tuberculosis infection in a patient.

Documented Applications

Use as sensors, therapeutic tools, to regulate cellular processes, and to guide drugs to specific cellular targets.

Use as immobilized capture elements in a microarray format.

Detection and quantification of LAM in body fluids or tissues or samples thereof for the purpose of detecting tuberculosis infection in a patient.

Use in fluorescence assays, electrochemical sensors, gold nanoparticle assays, enzyme linked aptamer sorbent assays (ELASA), pull down assays (immunoprecipitation), and microplate/well assays for detection.

Creation of aptamer beacons or aptabeacons (molecular beacons) that produce a detectable signal upon binding to a target molecule.

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