Systems and methods for discovering and optimizing lasso peptides
AssigneeLassogen, Inc.
InventorsMark J. Burk, I-Hsiung Brandon Chen
Life of this patent
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Abstract
Provided herein are lasso peptides libraries, and particularly molecular display libraries of lasso peptides. Also provided herein are related methods and systems for producing the libraries and for screening the libraries to identify candidate lasso peptides having desirable properties.
Claims91
A lasso peptide display library comprising a plurality of members, wherein each member comprises a lasso peptide or a functional fragment of lasso peptide;
- and wherein each member is associated with a unique identification mechanism for distinguishing the plurality of members from one another, wherein the unique identification mechanism is a unique nucleic acid molecule or a unique location.
A fusion protein comprising a lasso peptide component fused to a binding partner.
A method for evolving a lasso peptide of interest for a target property, the method comprising
- a. providing a first lasso peptide display library comprising members derived from the lasso peptide of interest, wherein each member of the first lasso peptide display library comprises at least one mutation to the lasso peptide of interest;
- b. subjecting the library to a first assay under a first condition to identify members having the target property;
- c. identifying the mutations of the identified members as beneficial mutations;
- and
- d. introducing the beneficial mutations into the lasso peptide of interest to provide an evolved lasso peptide.
A method for identifying a lasso peptide that specifically binds to a target molecule, the method comprising:
- providing a lasso peptide display library comprising a plurality of members, each member comprising a lasso peptide or a functional fragment of lasso peptide;
- contacting the library with the target molecule under a suitable condition that allows at least one member of the library to form a complex with the target molecule;
- and
- identifying the member of in the complex.
A method for identifying a lasso peptide that modulates a cellular activity, the method comprising
- a. providing a lasso peptide display library comprising a plurality of members, each member comprising a lasso peptide or a functional fragment of lasso peptide;
- b. subjecting the library to a suitable biological assay configured for measuring the cellular activity;
- c. detecting a change in the cellular activity;
- and
- d. identifying the members responsible for the detected change.
A method for identifying an agonist or antagonist lasso peptide for a target molecule, the method comprising:
- providing a lasso peptide display library comprising a plurality of members, each member comprising a lasso peptide or a functional fragment of lasso peptide;
- contacting the library with a cell expressing the target molecule under a suitable condition that allows at least one member of the library to bind to the target molecule;
- measuring a cellular activity mediated by the target molecule;
- and
- identifying the member as an agonist ligand for the target molecule if said cellular activity is increased;
- or identifying the member as an antagonist ligand if said cellular activity is decreased.
Dependencies are inferred from the claim text.