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.

Disclosed herein are methods of generating proteoglycans with distinct glycan structures in engineered, non-naturally occurring eukaryotic cells. These methods make accessible a dynamic range of protein glycosylation. Compositions of engineered, non-naturally occurring cells capable of generating these proteoglycans are also disclosed herein.

The present invention is directed to a bacterial, preferably probiotic bacterial peptidoglycan hydrolase (PGH), a peptidoglycan hydrolase (PGH)-comprising bacterial, preferably probiotic bacterial strain or a peptidoglycan hydrolase (PGH)-comprising composition for use in the therapeutic or prophylactic treatment of a bacterial infection, preferably for the treatment of a bacterial infection resulting in diarrhea. Further aspects of the present invention relate to corresponding methods for preparing a medicament and to a corresponding method of treatment.

Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibody provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in mucopolysaccharidosis IIIB (MPS-IIIB). The fusion antibodies provided herein comprise alpha-N-acetylgulcosaminidase (NAGLU). The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein.

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

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.

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.

Cleaning compositions may include at least 0.001 ppm of a polypeptide having hexosaminidase activity. The cleaning compositions may include a polypeptide having at least 60% sequence identity to the mature polypeptide shown in one or more of the motif(s) of SEQ ID NO 7, SEQ ID 8, SEQ ID 9, SEQ ID 10, SEQ ID 11, or combinations thereof. The cleaning compositions may be or include laundry detergents, fabric finishers, acidic cleaning agents, neutral cleaning agents, alkaline cleaning agents, hand dishwashing agents, automatic dishwasher compositions, or combinations thereof.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5 inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional human N-acetyl-alpha-glucosaminidase (hNAGLU), a regulatory sequence which direct expression of hNAGLU in a target cell, and an AAV 3 ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIB.

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.