Provided herein are recombinant glycoproteins (e.g., recombinant human α-galactosidase-A proteins) with an altered (e.g., improved) glycosylation profile, and pharmaceutical compositions and kits including one or more of these proteins. Also provided are methods of generating a mammalian cell useful for recombinant expression of a glycoprotein (e.g., recombinant human α-galactosidase-A), methods of producing recombinant glycoproteins, and methods of treatment that include administering to a subject at least one of the recombinant glycoproteins (e.g., recombinant human α-galactosidase-A protein).

The present invention relates to methods for purifying or enriching a biomolecule using multimodal resins and an elution buffer containing a Good's buffer.

The present disclosure provides codon optimized nucleotide sequences encoding human alpha-galactosidase A, vectors, and host cells comprising codon optimized alpha-galactosidase A sequences, and methods of treating disorders such as Fabry disease comprising administering to the subject a codon optimized sequence encoding human alpha-galactosidase A.

Proteins, nucleic acids encoding the proteins, compositions comprising the proteins, and methods are provided. The proteins have the ability to be self-targeted to ICAM-1 and, if desired, enzymatically-released at acidic pH. The ICAM-1-targeting peptides are provided as single copies or multiples repeats, and can be separated by linkers from the enzyme segment, from which the ICAM-1 targeting peptides can be released, if desired, at acidic pH. These fusion proteins enhance the activity of the enzyme segment within or liberated from the fusion protein, and provide increased recognition and targeting of diseased organs, transport from the bloodstream across the endothelium into said diseased organ, and intracellular uptake and lysosomal trafficking by cells in them, both in peripheral tissues and the central nervous system. Representative nucleotide and amino acid sequences of these fusion proteins, as well as in vitro, cellular, and in vivo animal data are provided. The described proteins can be used as a protein therapy, a gene therapy, or an implanted cell therapy.

Methods, compositions, and kits are provided for rapidly analyzing microbial growth and/or number in a plurality of water-in-oil emulsion droplets.

This disclosure relates to treatment of lysosomal storage disorders, such as Fabry disease or Gaucher disease, with a combination treatment containing (i) an mRNA encoding a lysosomal enzyme deficient in the lysosomal storage disorder, and (ii) a compound that is a glucosylceramide synthase inhibitor or a pharmacological chaperone of the lysosomal enzyme. mRNAs for use in the invention, when administered in vivo, encode the enzyme that is deficient in the lysosomal storage disorder, functional fragments thereof (e.g., those comprising the catalytic domain), or fusion proteins containing the enzyme that is deficient in the lysosomal storage disorder. mRNA therapies can be used to increase and/or restore deficient levels of a lysosomal enzyme's expression and/or activity in subjects.

The present invention relates to processes of producing a fermentation product from starch containing material comprising (a) forming a slurry comprising the starch-containing material and water; (b) converting the starch-containing material into dextrins with an alpha-amylase; (c) saccharifying the dextrins using a carbohydrate source generating enzyme to form sugars; (d) fermenting sugars using a fermenting organism; (e) recovering the fermentation product to form whole stillage; (f) separating the whole stillage into a liquid fraction thin stillage and solid fraction wet cake; (g) hydrolyzing the thin stillage; (h) recycle a portion of the hydrolyzed thin stillage to steps (a); wherein the thin stillage in step (g) is hydrolyzed using a glucoamylase and/or polygalacturonase.

Described are compositions comprising α-galactosidase A enzymes with unique carbohydrate profiles, as well as methods for manufacturing and purifying such enzymes. Also described methods of treating, preventing, and/or ameliorating Fabry Disease by administering such enzymes to a subject in need thereof. Also described are compositions comprising migalastat in combination with such α-galactosidase A enzymes.

Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.

Provided herein are methods for the treatment of lysosomal storage disease comprising administration of genes encoding for a lysosomal enzyme and a pharmaceutical agent. Combining gene therapy with pharmaceutical compositions by co-administration not only further enhances the effects of each individual therapy, but also provides a multi-faceted approach to treatment because of the varying mechanism of action of each individual composition.