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US 12,618,062 B2Granted
Display of molecules on silently genetically encoded nanoscale carriers for determining synergistic molecular interactions
Assignee48Hour Discovery Inc.
InventorsRatmir Derda, Nicholas Bennett, Susmita Sarkar
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Abstract
The present application provides a method of producing a “liquid” array of ligand (such as glycan) modified bacteriophage where the ligand modification is encoded genetically within the bacteriophage genome. This method will allow for the determination of the ligand binding profile of biomacromolecules and cells. Furthermore the method allows the elucidation of ligand-protein interactions where ligand binding is co-operative and synergistic.
Claims20
A method of identifying one or more molecular interactions between at least two ligands and a target molecule, the method comprising:
- (a) providing a plurality of silent carriers, each comprising one of a plurality of unique nucleic acid codes therein, wherein each silent carrier is externally chemically identical;
- (b) attaching a first glycan ligand to one set of silent carriers comprising a first nucleic acid code to form a first set of carriers;
- (c) repeating step (b) to produce N sets, where N>2, wherein each set comprises a different glycan ligand, or a different density of glycan ligand, and each set comprises a different nucleic acid code;
- (d) pooling the N sets to form a first mixed library comprising a liquid glycan array;
- (e) contacting the first mixed library with the target molecule and identifying the set of ligands {M} which bind to the target molecule;
- (f) repeatedly creating a pooled set of binding glycans, omitting one binding glycan or one density of binding glycan, to form different mixed libraries, and contacting each mixed library with the target model;
- and
- (g) determining, using the different nucleic acid codes, which binding glycans have lesser or greater affinity for the target molecule in the absence of the omitted glycan.
5 more elements
Dependencies are inferred from the claim text.