Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

The present disclosure relates to erythroid cells that have been engineered to comprise a uricase, a uric acid transporter, or both a uricase and a uric acid transporter. The engineered erythroid cells of the present disclosure are useful in degrading uric acid inside the engineered erythroid cell. The engineered erythroid cells of the present disclosure are useful in methods of treating hyperuricemia. The engineered erythroid cells of the present disclosure are also useful in methods of treating gout, and in particular chronic refractory gout.

Provided are an engineering probiotic for degrading uric acid, and a construction method therefor and the use thereof, which belongs to the field of biotechnology. The probiotic Escherichia coli Nissle 1917 is used as an original starting strain, and an exogenous gene is introduced into a genome thereof by means of genetic engineering technology for modification, such that uric acid can be efficiently and rapidly degraded; and it is proved by tests that the rapid degradation of uric acid can be achieved in the intestinal tract and blood of mice. Compared with current lactic acid bacteria for degrading uric acid in the market, the constructed engineering probiotic has a stronger degradation ability and a better treatment effect, and therefore has a good practical application value.

Provided are a red blood cell (RBC) having an agent linked thereto, wherein the agent is linked to at least one endogenous, non-engineered membrane protein of the RBC by a sortase-mediated glycine conjugation or lysine side chain ?-amino group conjugation, and wherein the agent comprises a uric acid degrading polypeptide, a uric acid transporter or the combination; a method for preparing the RBC; and the use of the RBC for preventing or treating a disorder, condition or disease associated with an elevated uric acid level including hyperuricemia or gout.

A recombinant nucleic acid molecule for making a circular RNA and a preparation method for the circular RNA are provided. The recombinant nucleic acid molecule comprises elements operably linked to each other and arranged, in a 5 to 3 direction, in the following order: (a) an intron fragment which includes a full-length intron; (b) an E2 fragment which includes a downstream exon of the full-length intron; (c) an internal ribosome entry site (IRES) fragment; (d) a urate oxidase coding fragment; and (e) an E1 fragment which includes an upstream exon of the full-length intron; wherein the full-length intron, the downstream exon, and the upstream exon are from a same gene.

Described are improved uricase sequences having beneficial effects and methods of treating patients suffering from hyperuricemia.

Disclosed herein are compositions and methods for reducing the antigenicity of molecules. The antigenicity of a molecule may be reduced or eliminated by conjugating at least one branched polymer to the molecule to form a molecule-polymer conjugate. The branched polymer may include a backbone and a plurality of side chains, each side chain covalently attached to the backbone.

Disclosed herein are compositions and methods for reducing the antigenicity of molecules, wherein the molecule comprises a uricase. The antigenicity of a molecule may be reduced or eliminated by conjugating at least one branched polymer to the molecule to form a molecule-polymer conjugate. The branched polymer may include a backbone and a plurality of side chains, each side chain covalently attached to the backbone.

Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

A method of treating a disease or disorder associated with excessive uric acid levels is disclosed herein. The method comprises administering to the subject by i.v. infusion an amount of a recombinant homotetrameric uricase enzyme comprising four uricase polypeptides having the amino acid sequence as set forth in SEQ ID NO: 2, wherein the polypeptides are crosslinked by polyethylene glycol (PEG) bis-aldehyde having a molecular weight of 2-3.5 kDa.