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.

A suspension useful for AAV9-mediated intrathecal and/or systemic delivery of an expression cassette containing a hIDS gene is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating Hunter syndrome and the symptoms associated with Hunter syndrome.

Certain embodiments provide a method of detecting one or more biomarkers in a subject having a lysosomal storage disorder, the method comprising: 1) measuring the concentration of a combination of two or more lipids in a sample from the subject, wherein the combination of lipids is selected from the group consisting of: a) a bis(monoacylglycero)phosphate (BMP); b) a GM2 ganglioside and/or a GM3 ganglioside; c) a GD3 ganglioside; d) a GD1a/b ganglioside; and e) a glucosylceramide (GlcCer); 2) measuring the concentration of GlcCer in a sample from the subject; 3) measuring the concentration of neurofilament light chain (Nf-L) in a sample from the subject; and/or 4) measuring the concentration of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in a sample from the subject.

Provided are adeno-associated virus (AAV) compositions that can restore IDS gene function in cells, and methods for using the these AAV compositions to treat disorders associated with reduction of IDS gene function (e.g., Hunter syndrome). Also provided are compositions, systems and methods for making the AAV compositions.

The present invention relates to an improved composition comprising purified fusion protein including an immunoglobulin and an iduronate-2-sulfatase (12S). In some embodiments, the fusion protein comprises at least about 60% conversion of the cysteine residue corresponding to Cys59 of SEQ ID NO:1 [wild-type human 12S] to C α-formylglycine (FGly), wherein the purified fusion protein is characterized with between 1% and 10% 2-mannose-6-phosphate (2-M6P) peak area on glycan map.

The present invention provides, among other things, improved substrate clearance assays for lysosomal enzyme that are particularly useful for measuring potency of lysosomal enzymes or other therapeutics for treatment of lysosomal storage diseases. In particular, the present invention combines a physiologically relevant substrate cell assay and an efficient scintillation based detection method.

A human CD40L-specific Tn3 molecule and therapeutic uses thereof.

The present invention relates to an implantable cell chamber device capable of retaining cells but permitting diffusion of biomolecules. Also disclosed are methods for delivering a therapeutic biomolecule to a subject in need thereof on a continuous or semi-continuous basis, by administering to the subject a cell chamber device comprising cells that secrete the therapeutic biomolecule.

Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic IDUA or IDS protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of MPS I or MPS II disease.

Methods and compositions for diagnosing, preventing or treating a viral infection in a subject comprising administering to a subject in need thereof an effective amount of a glycosidase or a sulfatase to degrade a glycan, such as heparan sulfate, to inhibit viral infection, such as COVID-19. Methods for identifying a glycosidase, a sulfatase, or a microbe associated with increased susceptibility to viral infection in a subject.