Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

The present invention provides compositions comprising one or more active pharmaceutical ingredients, wherein the compositions are in the form of high solids concentration pastes capable of being injected in relatively low volumes into an animal using standard commercially available syringes. The invention also provides methods of making such compositions, particularly those compositions comprising high molecular weight active ingredients (e.g., antibodies, enzymes and other proteins and peptides) at relatively high therapeutic concentrations in the high solids concentration pastes. The invention further provides methods of using such formulations in treating, preventing and/or ameliorating certain diseases and physical disorders in animals, including humans, in need thereof. The invention also provides kits comprising the formulations of the invention and a suitable syringe, which in some aspects may be pre-loaded or pre-filled with a composition of the invention.

Provided herein are gene therapy methods for the treatment of mucopolysaccharidosis type IV A (MPS IV A) involving the use of recombinant adeno-associated viruses (rAAVs) to deliver human N-acetylgalactosamine-6-sulfate sulfatase (hGALNS) to the bone of a human subject diagnosed with MPS IVA. Also provided herein are rAAVs that can be used in the gene therapy methods and methods of making such rAAVs.

Provided are chondrosulfatase and a use thereof, belonging to the technical field of biological engineering. Chondrosulfatase is screened and identified from the natural world, the maximum similarity between its amino acid sequence and that of the chondrosulfatase reported by NCBI being 85%; then the expression in Escherichia coli and Bacillus subtilis is optimized, achieving the high-efficiency biosynthesis of chondrosulfatase having high enzymatic activity, the maximum enzyme activity being 11976.5 U/L; furthermore, the entire process and post-processing are simpler. The invention has potentially broad value in application in the preparation of products containing low molecular-weight chondroitin sulfate in the fields of medicine, cosmetics, and biology, lays the foundation for efficient fermentation of a microbial system to produce a chondrosulfatase having high enzyme activity, and is suitable for industrialized production applications.

The present invention provides a new animal model for mucopolysaccharidosis type lVA or Morquio A syndrome and to methods of generating the animal model and uses thereof.

Provided are chondrosulfatase and a use thereof, belonging to the technical field of biological engineering. Chondrosulfatase is screened and identified from the natural world, the maximum similarity between its amino acid sequence and that of the chondrosulfatase reported by NCBI being 85%; then the expression in Escherichia coli and Bacillus subtilis is optimized, achieving the high-efficiency biosynthesis of chondrosulfatase having high enzymatic activity, the maximum enzyme activity being 11976.5 U/L; furthermore, the entire process and post-processing are simpler. The invention has potentially broad value in application in the preparation of products containing low molecular-weight chondroitin sulfate in the fields of medicine, cosmetics, and biology, lays the foundation for efficient fermentation of a microbial system to produce a chondrosulfatase having high enzyme activity, and is suitable for industrialized production applications.

Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

Provided herein are gene therapy methods for the treatment of mucopolysaccharidosis type IVA (MPS IVA) involving the use of recombinant adeno-associated viruses (rAAVs) to deliver human N-acetylgalactosamine-6-sulfate sulfatase (hGALNS) to the bone of a human subject diagnosed with MPS IVA. Also provided herein are rAAVs that can be used in the gene therapy methods and methods of making such rAAVs.

Compositions and methods for delivering enzymes in enzyme hydrogel formulations are disclosed. More particularly, the present disclosure relates to injectable enzyme hydrogel formulations and delivery of injectable enzyme hydrogel formulations. Also disclosed are methods for GALNS enzyme replacement therapy and lysosomal enzyme replacement therapy.

Compositions and methods for delivering enzymes in enzyme hydrogel formulations are disclosed. More particularly, the present disclosure relates to injectable enzyme hydrogel formulations and delivery of injectable enzyme hydrogel formulations. Also disclosed are methods for GALNS enzyme replacement therapy and lysosomal enzyme replacement therapy.