Provided herein are DNA vaccines for the treatment of peanut allergies. The vaccines comprise the coding sequence for one or more peanut allergenic epitopes fused in-frame with the luminal domain of the lysosomal associated membrane protein (LAMP) and the targeting sequence of LAMP. The vaccines can be multivalent molecules and/or can be provided as part of a multivalent vaccine comprising two or more DNA constructs.

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 invention provides compositions and methods for effective lysosomal targeting mediated by SORT1. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Sanfilippo syndrome type B.

Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

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.

A targeted therapeutic including a lysosomal enzyme and a lysosomal targeting moiety that is a peptide containing at least one N-linked glycosylation site. Methods of producing the targeted therapeutic may include nucleotide acids encoding the same and host cells co-expressing GNPT. Pharmaceutical compositions comprising the targeted therapeutic and methods of using the same to treat a lysosomal storage disease.

A fusion protein and a complex containing same, capable of being used for the intracellular delivery of cargo molecules. The fusion protein and complex can implement the efficient release of cargo molecules from endocytic vesicles, thereby significantly improving the cytoplasmic delivery efficiency of the cargo molecules. One cargo molecules can be obtained in cytoplasms, they can exert any function related thereto. The fusion protein and complex provide effective means for affecting biological mechanisms and pathways of cells, and can be used in various fields such as research, treatment, and diagnosis.

A peptide can have a sequence of one of SEQ ID NOs: 78-91. A conformationally-constrained kinked peptide includes: a conformationally-constraining portion and a kinked portion linked to the conformationally-constraining portion that conformationally constrains the kinked portion having a peptide sequence of one of SEQ NOs: 78-97. A cell-targeting compound can include a conformationally-constrained kinked peptide having a peptide sequence of one of SEQ ID NOs: 78-97. The peptide sequence can be one of SEQ ID NOs: 78-97, or 78-91, or 92-97. A cell-targeting compound can include a conformationally-constrained kinked peptide linked to a branched linker with one branch arm linked to a specific targeting moiety and one branch ann linked to a general targeting moiety. The specific targeting moiety can be an antibody. The general targeting moiety can be a lipid or cholesterol derivative.

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.

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.