Methods and compositions for developing spore display systems for medicinal and industrial applications
AssigneeMaxygen, Inc.
InventorsStanley Goldman, Stephanie J. Lathrop, Pascal F. Longchamp, Robert G. Whalen
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Abstract
Compositions and methods for utilizing spore systems for medicinal and industrial protein applications are provided. Compositions comprise spores that produce and/or display carbohydrates, proteins, peptides, and nucleic acids of interest. Such spores are useful as therapeutic or prophylactic agents or vaccines against a broad spectrum of immunogens and bacterial and viral pathogens. Additionally, spore systems are useful in production, packaging, delivery, and presentation of polypeptides and/or nucleic acids for industrial catalysts, medical applications, and diagnostic applications.
Claims121
A method for modulation of an immune response of an organism, said method comprising contacting said organism with a spore system comprising a recombinant spore having at least one exogenous nucleic acid, peptide, or polypeptide which modulates an immune response in the organism, wherein said spore is administered via a delivery system selected from the group consisting of respiratory delivery system, nasal delivery system, parenteral delivery system, and mucosal delivery system.
A method for modulation of an immune response of an organism, said method comprising contacting said organism with a spore system comprising a non-viable recombinant spore having at least one exogenous nucleic acid, peptide, or polypeptide which modulates an immune response in the organism.
A composition comprising a spore system, said spore system comprising a spore and at least one exogenous nucleic acid molecule, peptide, or polypeptide displayed on, bound to, or contained within said spore wherein said nucleic acid, peptide, or polypeptide modulates an immune response when administered to an organism via the respiratory delivery system, nasal delivery system, or the parenteral delivery system.
The composition of 26, wherein the nucleic acid, peptide, or polypeptide is displayed on or bound to the surface of the spore.
The composition of 26, wherein the peptide or polypeptide is produced as a fusion protein with a spore coat protein.
The composition of 28, wherein the spore coat protein is at least one protein selected from the group consisting of:
- CotA, CotB, CotC, CotD, CotE, CotF, CotG, CotN, CotS, CotT, CotV, CotW, CotX, CotY, and CotZ.
A composition comprising a spore system, said spore system comprising a spore, at least one antigen, and at least one adjuvant and/or co-stimulatory polypeptide.
A method for releasing a spore system of interest, said method comprising:
- a) transforming a cell that is capable of sporulation with an exogenous nucleic acid molecule;
- b) inducing sporulation of the cell, whereby at least one spore system is produced, said spore system comprising said nucleic acid molecule and/or any polypeptide produced therefrom, and a spore;
- and
- c) lysing the cell to release said spore system.
A method for displaying a polypeptide at one or more sites of interest on a surface of a spore, said method comprising:
- a) transforming a cell that is capable of sporulation with a recombinant nucleic acid vector comprising a nucleic acid molecule encoding a polypeptide fused in frame to a nucleic acid molecule encoding a spore coat protein;
- and
- b) expressing a fusion protein comprising said polypeptide and said spore coat protein such that said fusion protein is attached to the spore coat of the spore at one or more sites of interest on the surface of the spore.
A detection system comprising a spore system wherein said spore system comprises a moiety that provides a detectable signal and a polypeptide displayed on, bound to, or contained within the spore system, wherein said polypeptide is capable of capturing a detectable compound.
A method for delivery of a polypeptide of interest, said method comprising:
- a) transforming a cell that is capable of sporulating with a nucleic acid sequence encoding said polypeptide;
- b) inducing sporulation of said cell to form a spore;
- and
- c) delivering said spore to a site of interest.
A method for generating a desired product comprising reacting a substrate with a spore system, said spore system comprising a recombinant spore having at least one polypeptide wherein said polypeptide has enzymatic activity.
A composition comprising a spore system said spore system comprising a recombinant spore having at least one exogenous polypeptide wherein said polypeptide has enzymatic activity and a substrate wherein said enzyme alters said substrate.
A composition comprising a spore system, said spore system comprising a non-viable spore and at least one exogenous nucleic acid, peptide, or polypeptide displayed on, bound to, or contained within said spore.
A composition comprising a spore system, said spore system comprising a non-viable spore and one or more expression cassettes, wherein said one or more expression cassettes comprise a promoter operably linked to a nucleotide sequence of interest.
A method for modulation of an adjuvant effect in an organism, said method comprising:
- a) generating a non-viable spore, wherein said spore has an adjuvant effect;
- b) isolating said spore;
- and
- c) contacting said organism with said spore and a nucleic acid, peptide, or polypeptide.
A composition comprising a spore system, said spore system comprising a non-viable spore and one or more expression cassettes, wherein said expression cassettes are comprised of a promoter operably linked to a multiple cloning site.
A composition comprising a spore system, said spore system comprising a spore and at least one streptavidin or avidin molecule displayed on or bound to said spore.
A composition comprising a spore system, said spore system comprising a spore and at least one exogenous nucleic acid binding particle displayed on or bound to said spore.
A composition comprising a spore system, said spore system comprising a spore and at least one peptide, polypeptide, protein, carbohydrate, or nucleotide sequence having anti-pathogenic activity displayed on, bound to, or contained within said spore.
A method of enhancing an immune response to an immunogenic polypeptide or peptide in a subject, said method comprising administering to the subject a population of spores and an expression vector comprising a nucleotide sequence encoding the immunogenic polypeptide or peptide, wherein the immune response is enhanced compared to the immune response generated by administration of the expression vector or encoded immunogenic polypeptide or peptide alone to the subject.
A method of enhancing an immune response to an immunogenic polypeptide or peptide in a subject, said method comprising administering to the subject a population of spores and an immunogenic polypeptide or peptide, wherein the immune response to the immunogenic polypeptide or peptide is enhanced compared to the immune response generated by administration of the immunogenic polypeptide or peptide alone to the subject.
A composition comprising a spore system, said spore system comprising at least two spores wherein each spore displays a different peptide, polypeptide, or protein.
A composition comprising a spore system, said spore system comprising a spore and at least one rotavirus capsid protein displayed on, bound to, or contained within said spore.
Dependencies are inferred from the claim text.