Disclosed herein are methods for inducing immunity against a virus such as a coronavirus in the mucosal tissue of a patient, include administering a vaccine composition to the patient by oral administration (e.g., nasal injection, nasal inhalation, oral inhalation, and/or oral ingestion). Also disclosed are compositions for assaying the presence of anti-viral antibodies induced by the administered vaccine or the presence of viral proteins in a saliva sample include a stabilizing solution and may also include the use of aragonite particle beads. Compositions and methods are presented for prevention and/or treatment of a coronavirus disease wherein the composition comprises a recombinant entity. The recombinant entity is bivalent, comprising a nucleic acid encoding a coronavirus 2 nucleocapsid protein CoV2 nucleocapsid protein fused to an endosomal targeting sequence, and a nucleic acid encoding a CoV2 spike protein sequence optimized for cell surface expression.

Compositions and methods are described for a treatment of enduring viral infection in general, and long COVID in particular. The composition comprises T cells, antigen presenting cells (APC), and optionally NK cells derived from the whole blood of a patient. The APC are genetically engineered to comprise nucleic acids encoding antigenic peptide sequences for MHC-complexed cell surface expression, wherein further exposure to an IL-15 agonist and patient T cells yields activation and expansion of virally-educated T cells for re-administration to the patient, whereby cells harboring the virus are targeted for T-cell mediated cytotoxicity.

Compositions and methods for treating lysosomal storage diseases are disclosed. Biotherapeutic complexes containing an internalization effector binding domain and a lysosomal replacement enzyme activity are disclosed. The biotherapeutic complexes are capable of entering cells, segregating to the lysosome, and delivering the replacement enzyme activity to the lysosome.

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.

Disclosed herein are methods for inducing immunity against a virus such as a coronavirus in the mucosal tissue of a patient, include administering a vaccine composition to the patient by oral administration (e.g., nasal injection, nasal inhalation, oral inhalation, and/or oral ingestion). Also disclosed are compositions for assaying the presence of anti-viral antibodies induced by the administered vaccine or the presence of viral proteins in a saliva sample include a stabilizing solution and may also include the use of aragonite particle beads. Compositions and methods are presented for prevention and/or treatment of a coronavirus disease wherein the composition comprises comprises a recombinant entity. The recombinant entity is bivalent, comprising a nucleic acid encoding a coronavirus 2 nucleocapsid protein CoV2 nucleocapsid protein fused to an endosomal targeting sequence, and a nucleic acid encoding a CoV2 spike protein sequence optimized for cell surface expression.

Provided herein are compositions, systems, kits, and methods for treating nervous system injuries caused by trauma or neurodegeneration or aging in a subject by administering a CSPG or SOCS3 reduction peptide (CRP and SRP respectively), or a nucleic acid sequence encoding the CRP or SRP, wherein both the CRP and SRP comprise a cell membrane penetrating domain, and a lysosome targeting domain, and the CRP further comprises a chondroitin sulfate proteoglycan (CSPG) binding domain, and the SRP further comprises a suppressor of cytokine signaling-3 (SOCS3) binding domain.

The present invention relates to variants of acid-alpha glucosidase and uses thereof.

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase 1 and the CMPD is protein transduction domain of the HIV-1 Tat protein.

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 relates to fusion polypeptides comprising a sub-membrane targeting domain, a protein of interest or a functionally or structurally active fragment thereof, and a peptide interacting with the Endosomal Sorting Complexes Required for Transport (ESCRT) cellular machinery, and the use of said fusion polypeptides in methods of targeting a protein of interest in the lumen of an extracellular vesicle. The present invention also relates to extracellular vesicles comprising said fusion polypeptides, and their use for treating or preventing diseases.