The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A and B are nucleic acid sequences encoding a first and a second polypeptide of interest (POI); and X is a nucleic acid sequence which encodes a cleavage site, wherein either the first or second POI is a transmembrane protein which comprises an intracellular retention signal.

The present invention relates to (isolated) recombinant proteins, also referred to as improved MAT (iMAT) molecules, comprising at least one translocation module, at least one targeting module and at least one antigen module, wherein at least one cysteine residue is substituted with a different amino acid residue. Such iMAT molecules are useful specifically as vaccines, e.g., for therapy and/or prevention of allergies and/or infectious diseases and/or prevention of transmission of infectious diseases in equines. The present invention further relates to nucleic acids encoding such iMAT molecules, corresponding vectors and primary cells or cell lines.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Transgenic microalgae expressing at least one exogenous biologically active protein. The protein-expressing microalgae are used for the oral delivery of the biologically active protein to the target organism in its intact and functional form. The exogenous protein, expressed in algae, is characterized by being biologically active, exerting at least one specific activity having a beneficial effect on the subject consuming the algae. The transgenic microalgae are used as animal food for aquatic or land animals welfare or as food supplement for human healthcare.

In certain embodiments, the present disclosure provides compositions and methods for treating Forbes-Cori Disease.

The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (O interface); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (L domain); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (M domain), as well as membrane-enveloped versions of the multimeric assemblies.

The present invention provides anti-tau constructs. Anti-tau constructs of the invention are polynucleotide sequences encoding a polypeptide comprising at least one tau binding moiety and optionally comprising a signal peptide and/or a purification moiety. The present invention also provides isolated polypeptides encoded by anti-tau constructs, vectors comprising anti-tau constructs, and isolated cells comprising said vectors.

The invention relates to compounds, compositions, and methods for derepressing RE1 silencing transcription factor (REST) target genes are provided. In particular, a peptide having the sequence TEDLEPPEPPLPKEN (SEQ. ID NO: 1) and EDLEPPEPPLPK (SEQ. ID NO: 15), or the reversed sequences made of D-amino acids (retro inverted, RI) nekplppeppeldet (SEQ ID NO: 16) and kplppeppelde (SEQ ID NO: 17), are disclosed for inhibiting REST activity. The peptides are useful to treat, prevent, or ameliorate conditions such as traumatic brain injury, epilepsy, dementia, Huntington's Disease (HD), chronic pain, brain cancer (including glioblastoma multiforme), pancreatic cancer; diabetes, and peripheral nerve injury.

The present invention relates in general to therapeutic fusion proteins useful to treat lysosomal storage diseases and methods for treating such diseases. Exemplary therapeutic fusion proteins comprise a lysosomal enzyme, a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide. Also provided are compositions and methods for treating Mucopolysaccharidosis Type IIIB (Sanfilippo B Syndrome), comprising a targeted therapeutic fusion protein comprising alpha-N-acetylglucosaminidase (Naglu), a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide.

The present invention relates in general to therapeutic fusion proteins useful to treat lysosomal storage diseases and methods for treating such diseases. Exemplary therapeutic fusion proteins comprise a lysosomal enzyme, a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide. Also provided are compositions and methods for treating Mucopolysaccharidosis Type IIIB (Sanfilippo B Syndrome), comprising a targeted therapeutic fusion protein comprising alpha-N-acetylglucosaminidase (Naglu), a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide.