The present invention provides DNA vaccines for the treatment of allergies. The vaccines comprise the coding sequence for one or more allergenic epitopes, and preferably the full protein sequence, of the allergenic protein from which the epitope(s) is derived, fused inframe with the lumenal domain of the lysosomal associated membrane protein (LAMP) and the targeting sequence of LAMP. The vaccines allow for presentation of properly configured three dimensional epitopes for production of an immune response. The vaccines can be multivalent molecules, and/or can be provided as part of a multivalent vaccine containing two or more DNA constructs.

The invention provides compositions and methods for effective lysosomal targeting mediated by PCSK9. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Pompe Disease and Sanfilippo Syndrome Type B, and they may be used for targeting lysosomal enzymes to the various muscles of the human body.

Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.

The present disclosure provides for non-viral compositions and methods for delivering nucleic acids into eukaryotic cells (e.g., stem cells) with high efficiency and low genotoxicity.

Proteinaceous therapeutics, such as antibodies and fusion proteins, for preventing, reducing the occurrence of, and/or treating a SARS-CoV-2 infection in a subject are provided herein. The methods provided herein include administering to a subject an antigen binding fragments (Fab fragment) or antibody that binds to the S ARS-CoV-2 Spike protein, ACE2 decoy peptides that bind to the SAILS-CoV-2 Spike protein, and/or a DNA construct encoding an anti-Spike Fab fragment or ACE2 decoy peptide.

Provided herein is a construct comprising, in combination: an EphA3, EphA2 and/or EphB2 binding ligand; and at least one effector molecule. In some embodiments, the at least one effector molecule comprises a therapeutic agent, a nanoparticle, a detectable group, a lipid, or a liposome. In some embodiments, the construct is a fusion protein and/or a covalent conjugate. Further provided is a construct comprising, in combination: a ligand that binds to EphA2, EphA3 and/or EphB2; a ligand that binds to IL-13Rα2; and at least one effector molecule. Also provided are methods of use thereof for treating cancer.

Disclosed herein include methods, compositions, and kits suitable for use in vaccination. There are provided, in some embodiments, nucleic acid compositions (e.g., mRNA vaccine, DNA vaccine) comprising a polynucleotide encoding a fusion protein. The fusion protein can comprise an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD). A plurality of fusion proteins can be capable of self-assembling into an enveloped nanoparticle (ENP) secreted from a cell in which the fusion proteins are expressed. There are provided, in some embodiments, populations of ENPs.

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 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 EDLEPPEP-PLPK (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 amelio-rate 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

Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.