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.

Provided herein are compositions and methods of using a bicistronic vector for treating or preventing a lysosomal storage disorder (LSD) in a subject. The disclosed compositions comprise a bicistronic vector comprising a promoter, an Internal Ribosome Entry Site (IRES), a polynucleotide encoding a lysosomal enzyme and a polynucleotide encoding a modified GlcNAc-1 phosphotransferase (GlcNAc-1 PTase). The present methods comprise administering to the subject a pharmaceutical composition comprising the bicistronic vector as disclosed herein.

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.

This invention relates to viral vectors for delivery of α-N-acetylglucosaminidase (NAGLU) to a subject. In some aspects the NAGLU sequence is optimized for expression in human cells. The invention further relates to methods of using the vector to increase secretion of NAGLU from a cell and for treatment and prevention of mucopolysaccharidosis IIIB.

Provided herein are edible compositions for reducing semen viscosity and/or enhancing semen flavor, and methods of using and preparing such compositions.

The present disclosure provides AAV8 vectors and variants thereof that express nucleic acids sharing identity to a codon optimized NAGLU (coNAGLU) that improves transduction and distribution in brain cells and will improve disease outcomes in the Mucopolysaccharidoses IIIB (MPS IIIB) mouse model. The present disclosure also provides methods of treatment of a subject, and methods of transducing one or more brain cells, by administering these vectors, as well as uses of these vectors in the manufacture of medicaments for treatment. The present disclosure also provides compositions and host cells comprising rAAV vectors and rAAV particles that express a coNAGLU heterologous nucleic acid and confer enhanced transduction efficiency in human cells, such as brain cells (e.g., neurons). These compositions may be administered to a subject in need thereof.

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.

The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

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 iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.