Abstract: The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.

Abstract: The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.

Abstract: The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.

Abstract: The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.

Abstract: The present invention relates, in part, to methods and compositions for immunizing against infection by Chlamydia trachomatis. The methods and compositions rely, in part, on administering an immunogenic composition comprising one or more peptides derived from C. trachomatis major outer membrane protein (MOMP) to a subject to be immunized. In some embodiments, the compositions comprise a chimeric immunogens, expression vectors comprising the polynucleotides, and kits comprising the compositions are also provided.

Abstract: The present invention relates, in part, to methods and compositions for immunizing against infection by Chlamydia trachomatis. The methods and compositions rely, in part, on administering an immunogenic composition comprising one or more peptides derived from C. trachomatis major outer membrane protein (MOMP) to a subject to be immunized. In some embodiments, the compositions comprise a chimeric immunogens, expression vectors comprising the polynucleotides, and kits comprising the compositions are also provided.

Abstract: The present invention relates, in part, to methods and compositions for immunizing against infection by Chlamydia trachomatis. The methods and compositions rely, in part, on administering an immunogenic composition comprising one or more peptides derived from C. trachomatis major outer membrane protein (MOMP) to a subject to be immunized. In some embodiments, the compositions comprise a chimeric immunogen comprising a receptor binding domain, a translocation domain, and a Chlamydia trachomatis antigen. Polynucleotides encoding the chimeric immunogens, expression vectors comprising the polynucleotides, and kits comprising the compositions are also provided.

Abstract: This invention provides bioactive conjugates. The bioactive conjugates include: (1) a cell recognition moiety that binds to ?2 macroglobulin receptor ?2-MR and (2) a bioactive moiety which: (a) has a biological activity, (b) does not function solely as an immunogen to invoke an immune response and (c) does not have ADP ribosylating activity. The bioactive conjugates of this invention are useful in methods of transporting the bioactive moiety across a polar epithelial membrane. Thus, this invention provides methods for parenteral administration of proteins without injection.

Abstract: Methods and compositions for needleless delivery of macromolecules to the bloodstream of a subject are provided herein. In one aspect, the invention provides a delivery construct, comprising a receptor binding domain, a transcytosis domain, a macromolecule to be delivered to a subject, and a cleavable linker. In certain aspects, the cleavable linker can be cleavable by an enzyme present in higher concentration at or near the basal-lateral membrane of a polarized epithelial cell or in the plasma than elsewhere in the body, for example, at the apical side of the polarized epithelial cell. In other aspects, the invention provides nucleic acids encoding delivery constructs of the invention, kits comprising delivery constructs of the invention, cells expressing delivery constructs of the invention, and methods of using delivery constructs of the invention.

Abstract: The present invention relates, in part, to methods and compositions for needleless delivery of antibodies to a subject. The present invention also relates, in part, to methods for needleless delivery of fusion proteins comprising a bioactive molecule and an antibody fragment to subject. In one aspect, the methods and compositions involve administering to the subject a delivery construct comprising a carrier construct non-covalently bound to the antibody or fusion protein to be delivered, wherein the carrier construct comprises a receptor-binding domain, a transcytosis domain, and an antibody-binding domain to which the antibody or the antibody fragment of the fusion protein non-covalently binds.

Abstract: Disclosed are inhibitors of myosin light chain kinase, pharmaceutical compositions and kits comprising the inhibitors and methods of use.

Abstract: The present invention relates, in part, to methods and compositions for needleless delivery of antibodies to a subject. The present invention also relates, in part, to methods for needleless delivery of fusion proteins comprising a bioactive molecule and an antibody fragment to subject. In one aspect, the methods and compositions involve administering to the subject a delivery construct comprising a carrier construct non-covalently bound to the antibody or fusion protein to be delivered, wherein the carrier construct comprises a receptor-binding domain, a transcytosis domain, and an antibody-binding domain to which the antibody or the antibody fragment of the fusion protein non-covalently binds.

Abstract: Methods and compositions for needleless delivery of macromolecules to the bloodstream of a subject are provided herein. In one aspect, the invention provides a delivery construct, comprising a receptor binding domain, a transcytosis domain, a macromolecule to be delivered to a subject, and a cleavable linker. Generally, the cleavable linker is cleavable by an enzyme present in higher concentration at or near the basal-lateral membrane of a polarized epithelial cell or in the plasma than elsewhere in the body, for example, at the apical side of the polarized epithelial cell. In other aspects, the invention provides nucleic acids encoding delivery constructs of the invention, kits comprising delivery constructs of the invention, cells expressing delivery constructs of the invention, and methods of using delivery constructs of the invention.

Abstract: Methods and compositions for inducing an immune response against Pseudomonas aeruginosa are provided herein. In one aspect, the invention provides a chimeric immunogen, comprising a receptor binding domain, a translocation domain, and a Pseudomonas pilin peptide comprising an amino acid sequence that is TAADGLWKCTSDQDEQFIPKGCSK (SEQ ID NO.:1), wherein the chimeric immunogen, when administered to a subject, induces an immune response in said subject that is effective to reduce adherence of a microorganism that expresses said Pseudomonas pilin peptide to epithelial cells of said subject. In other aspects, the invention provides nucleic acids encoding chimeric immunogens of the invention, kits comprising chimeric immunogens of the invention, cells expressing chimeric immunogens of the invention, and methods of using chimeric immunogens of the invention.

Abstract: Methods and compositions for inducing an immune response against Pseudomonas aeruginosa are provided herein. In one aspect, the invention provides a chimeric immunogen, comprising a receptor binding domain, a translocation domain, and a Pseudomonas pilin peptide comprising an amino acid sequence that is TAADGLWKCTSDQDEQFIPKGCSK (SEQ ID NO.:1), wherein the chimeric immunogen, when administered to a subject, induces an immune response in said subject that is effective to reduce adherence of a microorganism that expresses said Pseudomonas pilin peptide to epithelial cells of said subject. In other aspects, the invention provides nucleic acids encoding chimeric immunogens of the invention, kits comprising chimeric immunogens of the invention, cells expressing chimeric immunogens of the invention, and methods of using chimeric immunogens of the invention.

Abstract: Disclosed are inhibitors of myosin light chain kinase, pharmaceutical compositions and kits comprising the inhibitors and methods of use.

Abstract: The present invention relates, in part, to methods and compositions for immunizing against infection by Chlamydia trachomatis. The methods and compositions rely, in part, on administering an immunogenic composition comprising one or more peptides derived from C. trachomatis major outer membrane protein (MOMP) to a subject to be immunized. In some embodiments, the compositions comprise a chimeric immunogen comprising a receptor binding domain, a translocation domain, and a Chlamydia trachomatis antigen. Polynucleotides encoding the chimeric immunogens, expression vectors comprising the polynucleotides, and kits comprising the compositions are also provided.

Abstract: Methods and compositions for inducing an immune response against multiple antigens are provided herein. In one aspect, the invention provides a chimeric immunogen, comprising a receptor binding domain, a translocation domain, and more than one non-contiguous heterologous antigen. In other aspects, the invention provides nucleic acids encoding chimeric immunogens of the invention, kits comprising chimeric immunogens of the invention, cells expressing chimeric immunogens of the invention, and methods or using chimeric immunogens of the invention.

Abstract: The present invention relates, in part, to methods and compositions for needleless delivery of macromolecules to a subject. In one aspect, the methods and compositions involve administering to the subject a delivery construct comprising a carrier construct non-covalently bound to a binding partner, wherein the carrier construct comprises a receptor-binding domain, a transcytosis domain, and a macromolecule to which the binding partner non-covalently binds, wherein the binding partner binds to the macromolecule with a Ka that is at least about 104 M?1.

Abstract: Methods and compositions for needleless delivery of particles to the bloodstream of a subject are provided herein. In one aspect, the invention provides a delivery construct, comprising a receptor binding domain, a transcytosis domain, a particle to be delivered to a subject, and, optionally, a cleavable linker. In other aspects, the invention provides compositions comprising delivery constructs of the invention, kits comprising delivery constructs of the invention, and methods of using delivery constructs of the invention.