Proteins, protein fragments, nucleic acids and vectors derived from Neisseria gonorrhoeae, as well as to methods of inducing immunity against N. gonorrhoeae. Also disclosed are antibodies binding to the proteins and protein fragments.

The present invention relates to a peptide and its use as a medicament, in particular in the treatment of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD) or cholestatic liver disease.

The compounds disclosed herein compound of Formula (I), substructures thereof, and pharmaceutically acceptable salts thereof. The compounds provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

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This disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and/or PFKFB4 has beneficial effect as well as neuroprotection.

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

Provided is a fusion polypeptide comprising GDF15 (Growth/differentiation factor 15) and an Fc region of immunoglobulin, a pharmaceutical composition comprising the fusion polypeptide, and a method of increasing in vivo duration of GDF15 comprising fusing with an Fc region of immunoglobulin.

The present invention relates to a biotin moiety-conjugated polypeptide and a pharmaceutical composition for oral administration comprising the same, wherein the polypeptide according to the present invention has an excellent in vivo oral bioavailability.

The present invention provides, among other things, effective methods and compositions for delivering messenger RNA (mRNA) via rectal delivery. The present invention is, in part, based on unexpected observation that mRNA may be effectively delivered to the circulation, liver, kidney, colon and/or rectum via rectal delivery despite the barriers such as RNase and mucus layer.

Disclosed herein are recombinant AAV variant (e.g., variant serotype 3B (AAV3B)) capsid proteins and variant capsid protein-containing viral particles with enhanced ability to transduce hepatic cells. Viral particles containing these capsid variants are capable of evading neutralization by the host humoral immune response. The recombinant AAV3B variant proteins and viral particles disclosed herein were identified from a variant AAV3B capsid library that was engineered by making substitutions in only the variable regions of the capsid. Some embodiments of the AAV3B capsid variants disclosed herein comprise the AAV3B-G3 variant and the AAV3B-E12 variant. Compositions of these variant AAV particles are provided that are useful for transducing and delivering therapeutic transgenes to cells, such as liver cells, and thus treat diseases and disorders pertaining to these cells.

Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.