Uricase-encoding mrna, and composition thereof and use thereof

Abstract

Provided are a uricase-encoding mRNA, and a composition thereof and the use thereof. The mRNA is obtained from an ORF sequence with a high protein expression level by means of codon optimization and screening, and combinatorial screening of 5' UTR and 3' UTR. The mRNA can be expressed in an animal to produce uricases, so that uric acids in the animal can be oxidized into allantoic acids, and the content of uric acids in the animal is reduced, thereby avoiding the occurrence of hyperuricemia and gout symptoms.

Description

mRNA encoding uricase, its composition and applications This application claims priority to Chinese patent application 2025101190336, filed on January 24, 2025. The entire contents of the aforementioned Chinese patent application are incorporated herein by reference. Technical Field This invention relates to the field of biopharmaceutical technology, and more specifically, to mRNAs encoding uricases of different species, their compositions, and applications. Background Technology Hyperuricemia (HUA) refers to an excess of uric acid production and / or insufficient excretion in the body under normal dietary conditions. Hyperuricemia is defined as a fasting blood uric acid level exceeding 420 μmol / L in men and exceeding 360 μmol / L in women on two separate occasions. High uric acid levels can lead to the deposition of urate crystals in the joints, causing gout. Uricase is an enzyme involved in the metabolic pathway of purine degradation in organisms. It rapidly oxidizes uric acid into allantoic acid, preventing its reabsorption by the renal tubules and its excretion. It is effective in treating nodular gout, urinary stones, and hyperuricemia caused by renal failure. Uricase is present in many species, but it is lacking in humans and some primates. In recent years, uricases from various mammalian and microbial sources have been widely used in genetic engineering to express and produce recombinant uricases. Currently, two recombinant uricase products are available in Europe and the United States: raburicase and pegloticase. Raburicase, derived from Aspergillus flavus, was approved by the US FDA in July 2002. However, this drug is quite expensive and has a short half-life (only 18 hours), requiring daily injections, with a treatment duration of generally 5-7 days. Pegloticase (Krystexxa) is a PEGylated recombinant uricase, launched in the United States in 2010 and subsequently approved by the European Union for the treatment of refractory gout that does not respond well to traditional uric acid-lowering methods. Although the dosing cycle of pegloticase is extended to once every two weeks compared to raburicase, its price remains quite high, far exceeding the affordability of most patients. With the advancement of science and technology, mRNA drugs have become a major research focus due to their numerous advantages, such as the absence of risk of genome integration, direct and rapid translation into proteins, high safety, natural metabolites, and low toxicity. Furthermore, mRNA is convenient and quick to produce, with low production costs, and its long expression time allows for reduced dosing frequency. Therefore, compared to protein drugs, mRNA drugs offer lower dosage, lower dosing frequency, and lower cost while achieving the same therapeutic effect. However, there are currently no reports on mRNA drugs that regulate uricase expression. Summary of the Invention The purpose of this invention is to provide mRNAs encoding uricases from different species. Another object of the present invention is to provide a composition comprising mRNA encoding uricase and / or uricase fusion proteins of different species. Another object of the present invention is to provide the use of mRNA comprising encoding uricase and / or uricase fusion proteins of different species. The above-mentioned objective of the present invention is achieved by the following solution: An mRNA encoding uricase, comprising a coding region, wherein the coding region contains one or more ORFs; the ORFs are selected from SEQ ID NO:20-39 or sequences having at least 95% similarity to one of SEQ ID NO:20-39. In one embodiment, the ORF is selected from SEQ ID NO:20-39 or a sequence that has at least 98% similarity to one of SEQ ID NO:20-39. In one embodiment, when the coding region contains at least two ORFs, the sequences of the ORFs may be the same or different; each ORF is separated by any one of the sequences in SEQ ID NO:40-41. In one embodiment, when the coding region contains at least two ORFs, each ORF is selected from SEQ ID NO:20-39 or a sequence that is at least 98% similar to one of SEQ ID NO:20-39. In one implementation, when the coding region contains at least three ORFs, the interval sequences may be the same or different. In one embodiment, when the coding region contains at least three ORFs, each ORF is selected from SEQ ID NO:20-39 or a sequence that is at least 98% similar to one of SEQ ID NO:20-39. In one embodiment, the ORF is selected from SEQ ID NO:20-27, SEQ ID NO:36-39, or a sequence that has at least 98% similarity to one of SEQ ID NO:20-27 or SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:20-27 and SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:24-27, SEQ ID NO:36-39, or a sequence that has at least 98% similarity to one of SEQ ID NO:24-27 or SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:24-27 and SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:24, SEQ ID NO:36-39, or a sequence that has at least 98% similarity to one of SEQ ID NO:24 or SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:36-39 or a sequence that has at least 98% similarity to one of SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:36-39. Preferably, the ORF is selected from one of SEQ ID NO:24, 36, 37, 38, 39. Preferably, the ORF is selected from one of SEQ ID NO:36, 37, 38, 39. Preferably, the ORF is selected from one of SEQ ID NO:36, 38, 39. Preferably, the ORF is one of SEQ ID NO:37, 38, and 39. In one embodiment, the ORF is SEQ ID NO:24. In one implementation, the ORF is SEQ ID NO:36. In one implementation, the ORF is SEQ ID NO:37. In one implementation, the ORF is SEQ ID NO:38. In one implementation, the ORF is SEQ ID NO:39. In one embodiment, the mRNA further includes a 5'UTR, the sequence of which is selected from any one of SEQ ID NO:1-15 and SEQ ID NO:42. Preferably, 5'UTR is selected from one of SEQ ID NO:3 and 42. In one embodiment, the mRNA further includes a 3'UTR, the sequence of which is selected from any one of SEQ ID NO:16-19 and SEQ ID NO:43. Preferably, 3'UTR is selected from one of SEQ ID NO:16 and 43. In one embodiment, the mRNA also includes polyA, which contains at least 70 adenosine molecules. In one embodiment, poly A contains 70-140 adenosine, or 70-120 adenosine, or 80-120 adenosine, or 90-120 adenosine, or 100-140 adenosine, or 100-120 adenosine. In one embodiment, the mRNA includes: (ii) 5'UTR; the 5'UTR is selected from any one of SEQ ID NO:1-15, SEQ ID NO:42; (iii) A coding region; the coding region contains one or more ORFs; the ORFs are selected from SEQ ID NO:20-39 or sequences that are at least 95% similar to one of SEQ ID NO:20-39; (iv) 3'UTR; the 3'UTR is selected from any one of SEQ ID NO:16-19 and SEQ ID NO:43; (v)poly A; the poly A contains at least 70 adenosine molecules. In one embodiment, when the coding region contains at least two ORFs, the sequences of the ORFs may be the same or different; each ORF is separated by any one of the sequences in SEQ ID NO:40 or SEQ ID NO:41 as a spacer sequence. In one implementation, when the coding region contains at least three ORFs, the interval sequences may be the same or different. In one embodiment, when the coding region contains at least two ORFs, each ORF is selected from SEQ ID NO:20-39 or a sequence that is at least 98% similar to one of SEQ ID NO:20-39. In one embodiment, poly A contains 70-140 adenosine, or 70-120 adenosine, or 80-120 adenosine, or 90-120 adenosine, or 90-110 adenosine, or 90-100 adenosine, or 100-140 adenosine, or 100-120 adenosine, or 90-110 adenosine. Preferably, poly A contains 70-140 adenosine molecules. Preferably, poly A contains 70-120 adenosine molecules. Preferably, poly A contains 80-120 adenosine molecules. Preferably, poly A contains 90-120 adenosine molecules. Preferably, poly A contains 90-110 adenosine molecules. Preferably, poly A contains 90-100 adenosine molecules. Preferably, poly A contains 100-140 adenosine molecules. Preferably, poly A contains 100-120 adenosine molecules. Preferably, poly A contains 100-110 adenosine molecules. In one embodiment, the ORF is selected from SEQ ID NO:20-27, SEQ ID NO:36-39, or a sequence that has at least 98% similarity to one of SEQ ID NO:20-27 or SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:20-27 and SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:24-27, SEQ ID NO:36-39, or a sequence that has at least 98% similarity to one of SEQ ID NO:24-27 or SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:24-27 and SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:24, SEQ ID NO:36-39, or a sequence that has at least 98% similarity to one of SEQ ID NO:24 or SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:36-39 or a sequence that has at least 98% similarity to one of SEQ ID NO:36-39. Preferably, the ORF is selected from SEQ ID NO:36-39. Preferably, the ORF is selected from one of SEQ ID NO:24, 36, 37, 38, 39. Preferably, the ORF is selected from one of SEQ ID NO:36, 37, 38, 39. Preferably, the ORF is selected from one of SEQ ID NO:36, 38, 39. Preferably, the ORF is one of SEQ ID NO:37, 38, and 39. In one embodiment, the ORF is SEQ ID NO:24. In one implementation, the ORF is SEQ ID NO:36. In one implementation, the ORF is SEQ ID NO:37. In one implementation, the ORF is SEQ ID NO:38. In one implementation, the ORF is SEQ ID NO:39. In one embodiment, the mRNA sequence is SEQ ID NO:157, SEQ ID NO:247, SEQ ID NO:261-265. Preferably, the mRNA sequence is SEQ ID NO:247, SEQ ID NO:261-265; Preferably, the mRNA sequence is SEQ ID NO:261-265. Preferably, the mRNA sequence is SEQ ID NO:247 or SEQ ID NO:262-265. Preferably, the mRNA sequence is SEQ ID NO:262-265. Preferably, the mRNA sequence is SEQ ID NO:247 or SEQ ID NO:262. Preferably, the mRNA sequence is SEQ ID NO:262. Preferably, the mRNA sequence is SEQ ID NO:263. Preferably, the mRNA sequence is SEQ ID NO:264. Preferably, the mRNA sequence is SEQ ID NO:265. In one embodiment, the amino acid sequence encoded by the mRNA contains one of SEQ ID NO:58-64. Preferably, the amino acid sequence encoded by the mRNA contains one of SEQ ID NO:59, 62-64. Preferably, the amino acid sequence encoded by the mRNA contains one of SEQ ID NO:62-64. Preferably, the amino acid sequence encoded by the mRNA contains one of SEQ ID NO:59, 62, 63. Preferably, the amino acid sequence encoded by the mRNA contains one of SEQ ID NO:59, 62, 64. Preferably, the amino acid sequence encoded by the mRNA contains one of SEQ ID NO:59, 63, 64. Preferably, the amino acid sequence encoded by the mRNA contains SEQ ID NO:59. Preferably, the amino acid sequence encoded by the mRNA includes SEQ ID NO:62. Preferably, the amino acid sequence encoded by the mRNA contains SEQ ID NO:63. Preferably, the amino acid sequence encoded by the mRNA contains SEQ ID NO:64. In one embodiment, the mRNA further includes (i) a 5' cap structure, the 5' cap structure being selected from Cap0, Cap1, Cap2 or the structure shown in Formula I: Where R1 represents H and C1-4 Alkyl, C 1-4 Halogenated alkyl, phenyl, C 1-4 Alkyl-substituted phenyl, halophenyl, benzyl, C 1-4 Alkyl-substituted benzyl or halobenzyl; R2 is OH, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Alkoxy-substituted C 1-4 Alkyl, C 1-4 Alkylamine substituent C 1-4 Alkyl, C 1-4 Amide group substituted C 1-4 Alkyl, benzyloxy, halobenzyloxy, benzyloxy-substituted C 1-4 Alkyl or halobenzyloxy-substituted C 1-4 alkyl; R3 and R4 are independently H and C. 1-4 Alkyl or C 1-4 Halogenated alkyl groups; R5 represents H and C. 1-4 Alkoxy, F, Cl, I, or N3; R6 represents H and C. 1-4 Alkyl, C 1-4 alkenyl, C 1-4 alkynyl, phenyl, C 1-4 Alkyl-substituted phenyl, halophenyl, benzyl, C 1-4 Alkyl-substituted benzyl or halobenzyl; B1 and B2 are each independently a base G, A, U or C, and substituted bases include, but are not limited to, 6-MeA, 5-MeU or 5-MeC. In one embodiment, R6 is H or C. 1-4 Alkyl, C 1-4 alkenyl, C 1-4 Alkyne, phenyl, halophenyl, benzyl, or halobenzyl. In one embodiment, R6 is H or C. 1-4 Alkyl, phenyl, halophenyl, benzyl or halobenzyl. In one embodiment, R6 is H, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, phenyl, benzyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 3-fluorobenzyl, 4-fluorobenzyl, 3,5-difluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl or 3,5-dichlorobenzyl. In one embodiment, R6 is H, methyl, ethyl, propyl, isopropyl, phenyl, benzyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl. In one embodiment, R6 is H, methyl, ethyl, isopropyl, phenyl, benzyl, 4-fluorophenyl, 4-chlorophenyl, 4-fluorobenzyl or 4-chlorobenzyl. In one embodiment, R6 is H, methyl, ethyl, isopropyl, phenyl, benzyl, 4-fluorophenyl, or 4-fluorobenzyl. In one embodiment, R6 is H or methyl. In one embodiment, R6 is phenyl or 4-fluorophenyl. In one embodiment, R6 is benzyl or 4-fluorobenzyl. In one embodiment, R5 is H, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, F, Cl, I, or N3. In one embodiment, R5 is H, methyl, ethyl, propyl, isopropyl, tert-butyl, F, or N3. In one embodiment, R5 is H, methyl, ethyl, isopropyl, F, or N3. In one embodiment, R5 is H, methyl, ethyl, F, or N3. In one implementation, R5 is H or F. In one embodiment, R5 is H or methyl. In one implementation, R5 is F or N3. In one embodiment, R3 and R4 are each independently H, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, or trifluoroisopropyl. In one embodiment, R3 and R4 are each independently H, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, trifluoroethyl, or trifluoroisopropyl. In one embodiment, R3 and R4 are each independently H, methyl, ethyl, isopropyl, trifluoromethyl, or trifluoroethyl. In one embodiment, R3 and R4 are each independently H, methyl, ethyl, or trifluoromethyl. In one embodiment, R3 and R4 are each independently H, methyl, or trifluoromethyl. In one embodiment, R2 is OH or C. 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Alkoxy-substituted C1-4 Alkyl, C 1-4 Alkylamine substituent C 1-4 Alkyl, C 1-4 Amide group substituted C 1-4 Alkyl, benzyloxy or benzyloxy-substituted C 1-4 alkyl. In one embodiment, R2 is OH or C. 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-3 Alkoxy-substituted C 1-3 Alkyl, C 1-3 Alkylamine substituent C 1-3 Alkyl, C 1-3 Amide group substituted C 1-3 Alkyl, benzyloxy or benzyloxy-substituted C 1-3 alkyl. In one embodiment, R2 is OH or C. 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-3 Alkoxy-substituted C 1-3 Alkyl, C 1-3 Alkylamine substituent C 1-3 Alkyl or C 1-3 Amide group substituted C 1-3 alkyl. In one embodiment, R2 is OH or C. 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkyl or C 1-3 Alkoxy-substituted C 1-3 alkyl. In one embodiment, R2 is OH, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, methyloxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoroisopropyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxyisopropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxyisopropyl, propoxymethyl, propoxyethyl, isopropoxymethyl, or isopropoxyethyl. In one embodiment, R2 is OH, methyl, ethyl, propyl, isopropyl, tert-butyl, methyloxy, ethoxy, propoxy, isopropoxy, tert-butoxy, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoroisopropyl, methoxymethyl, methoxyethyl, methoxyisopropyl, ethoxymethyl, ethoxyethyl, ethoxyisopropyl, propoxymethyl, propoxyethyl, isopropoxymethyl, or isopropoxyethyl. In one embodiment, R2 is OH, methyl, ethyl, methyloxy, ethoxy, isopropoxy, tert-butoxy, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoroisopropyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, propoxyethyl, isopropoxymethyl, or isopropoxyethyl. In one embodiment, R2 is OH, methyl, ethyl, methyloxy, ethoxy, trifluoromethyl, trifluoroethyl, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, propoxyethyl, isopropoxymethyl, or isopropoxyethyl. In one embodiment, R2 is OH, methyloxy, ethoxy, trifluoromethyl, methoxymethyl, or ethoxymethyl. In one embodiment, R2 is OH, methyloxy, or methoxymethyl. In one embodiment, R2 is -CH2NHCH3, -CH2NHC2H5, -CH2NHC3H7, -CH2NHC4H9, -C2H4NHCH3, -C2H4NHC2H5, -C2H4NHC3H7, -C2H4NHC4H9, -C3H6NHCH3, -C3H6NHC2H5, -C3H6NHC3H7, -C3H6NHC4H9, -CH2NHCOCH3, -CH2NHCOC2H5, -CH2NHCOC3H7, -C2H4NHCOC2H5, or -C2H4NHCOC3H7. In one embodiment, R2 is -CH2NHCH3, -CH2NHC2H5, -CH2NHC3H7, -C2H4NHCH3, -C2H4NHC2H5, -C2H4NHC3H7, -C3H6NHCH3, -C3H6NHC2H5, -C3H6NHC3H7, -CH2NHCOCH3, -CH2NHCOC2H5, -CH2NHCOC3H7, or -C2H4NHCOC2H5. In one embodiment, R2 is -CH2NHCH3, -CH2NHC2H5, -CH2NHC3H7, -C2H4NHCH3, -C2H4NHC2H5, -C3H6NHCH3, -C3H6NHC2H5, -CH2NHCOCH3, -CH2NHCOC2H5, or -C2H4NHCOC2H5. In one embodiment, R2 is -CH2NHCH3, -CH2NHC2H5, -CH2NHC3H7, -C2H4NHCH3, -C2H4NHC2H5, -CH2NHCOCH3, or -CH2NHCOC2H5. In one embodiment, R2 is -CH2NHCH3, -CH2NHC2H5, -CH2NHC3H7, -CH2NHCOCH3, or -CH2NHCOC2H5. In one embodiment, R2 is CH2NHCOCH3 or -CH2NHCOC2H5. In one embodiment, R1 is H, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoroisopropyl, phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 2,6-dimethyl-phenyl, 3,5-dimethyl-phenyl, 2-ethyl-phenyl, 3-ethyl-phenyl, 4-ethyl-phenyl, 2,6-diethyl-phenyl, 3,5-diethyl-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,6-chloro-phenyl, 3,5-chloro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl -Phenyl, 4-fluoro-phenyl, 2,6-fluoro-phenyl, 3,5-fluoro-phenyl, benzyl, 2-methyl-benzyl, 3-methyl-benzyl, 4-methyl-benzyl, 2,6-dimethyl-benzyl, 3,5-dimethyl-benzyl, 2-ethyl-benzyl, 3-ethyl-benzyl, 4-ethyl-benzyl, 2,6-diethyl-benzyl, 3,5-diethyl-benzyl, 2-chloro-benzyl, 3-chloro-benzyl, 4-chloro-benzyl, 2,6-chloro-benzyl, 3,5-chloro-benzyl, 2-fluoro-benzyl, 3-fluoro-benzyl, 4-fluoro-benzyl, 2,6-fluoro-benzyl or 3,5-fluoro-benzyl. In one embodiment, R1 is H, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoroisopropyl, phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3,5-dimethyl-phenyl, 3-ethyl-phenyl, 4-ethyl-phenyl, 3,5-diethyl-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 3,5-chloro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3,5-fluoro-phenyl, benzyl, 3-methyl-benzyl, 4-methyl-benzyl, 3,5-dimethyl-benzyl, 3-ethyl-benzyl, 4-ethyl-benzyl, 3,5-diethyl-benzyl, 3-chloro-benzyl, 4-chloro-benzyl, 3,5-chloro-benzyl, 3-fluoro-benzyl, 4-fluoro-benzyl, or 3,5-fluoro-benzyl. In one embodiment, R1 is H, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, trifluoroethyl, trifluoroisopropyl, phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3,5-dimethyl-phenyl, 4-ethyl-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, benzyl, 3-methyl-benzyl, 4-methyl-benzyl, 3-ethyl-benzyl, 4-ethyl-benzyl, 3-chloro-benzyl, 4-chloro-benzyl, 3-fluoro-benzyl, or 4-fluoro-benzyl. In one embodiment, R1 is H, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, trifluoroethyl, trifluoroisopropyl, phenyl, 4-methyl-phenyl, 4-ethyl-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, benzyl, 4-methyl-benzyl, 4-ethyl-benzyl, 4-chloro-benzyl or 4-fluoro-benzyl. In one embodiment, R1 is H, methyl, ethyl, isopropyl, trifluoromethyl, trifluoroethyl, benzyl, 4-methyl-benzyl, 4-ethyl-benzyl, 4-chloro-benzyl, or 4-fluoro-benzyl. In one embodiment, R1 is H, methyl, ethyl, isopropyl, trifluoromethyl, trifluoroethyl, benzyl, 4-methyl-benzyl, or 4-fluoro-benzyl. In one embodiment, R1 is methyl, ethyl, isopropyl, trifluoromethyl, benzyl, 4-methyl-benzyl, or 4-fluoro-benzyl. In one embodiment, R1 is methyl, benzyl, 4-methyl-benzyl, or 4-fluoro-benzyl. In one embodiment, R1 is methyl, benzyl, or 4-methyl-benzyl. In one embodiment, R1 is methyl, benzyl, or 4-fluoro-benzyl. In some embodiments, the 5' cap structure can be, but is not limited to, the following compounds: In one embodiment, the mRNA comprises at least one chemically modified nucleoside. In one embodiment, the chemically modified nucleoside is selected from pseudouracil, N1-methyl-pseudouracil, 1-ethylpseudouracil, 2-thiouracil, 4'-thiouracil, 5-methyluracil, or 5-methoxyuracil, or any combination thereof. In one embodiment, the chemically modified nucleoside is selected from pseudouracil. In one embodiment, the chemically modified nucleoside is selected from N1-methyl-pseuuridine. In one embodiment, the chemically modified nucleoside is selected from pseudouracil and / or N1-methyl-pseudouracil. In one embodiment, the chemically modified nucleoside is selected from 1-ethylpseuuridine. In one embodiment, the chemically modified nucleoside is selected from 1-ethylpseudouracil and / or N1-methylpseudouracil. In one embodiment, the chemically modified nucleoside is selected from 1-ethylpseudouracil and / or pseudouracil. In one embodiment, the chemically modified nucleoside is selected from 4'-thiouracil. In one embodiment, the chemically modified nucleoside is selected from 4'-thiouracil and / or N1-methyl-pseuuridine. In one embodiment, the chemically modified nucleoside is selected from 4'-thiouracil and / or pseudouracil. In one embodiment, the chemically modified nucleoside is selected from 5-methyluracil. In one embodiment, the chemically modified nucleoside is selected from 5-methyluracil and / or N1-methyl-pseuuridine. In one embodiment, the chemically modified nucleoside is selected from 5-methyluracil and / or pseudouracil. In one embodiment, the chemically modified nucleoside is selected from 5-methoxyuracil. In one embodiment, the chemically modified nucleoside is selected from 5-methoxyuracil and / or N1-methyl-pseuuridine. In one embodiment, the chemically modified nucleoside is selected from 5-methoxyuracil and / or pseudouracil. In one embodiment, the percentage of chemically modified nucleosides in the mRNA is 10–100%, or 20–100%, or 30–100%, or 40–100%, or 50–100%, or 60–100%, or 70–100%, or 80–100%, or 90–100%, or 50–98%, or 50–95%, or 60–95%, or 70–95%, or 80–95%, or 90–95%, or 70–90%, or 80–90%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 10-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 20% to 100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 30% to 100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 40-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 50-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 60-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 70-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 80-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 90-100%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 50-98%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 50-95%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 60-95%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 70-95%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 80-95%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 90-95%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 70-90%. In one embodiment, the proportion of chemically modified nucleosides in the mRNA is 80-90%. In one embodiment, the amino acid sequence encoded by the mRNA comprises SEQ ID NO:5001-5020. In one embodiment, the amino acid sequence encoded by the mRNA comprises SEQ ID NO:5001-5004. In one embodiment, the amino acid sequence encoded by the mRNA contains SEQ ID NO:5002. In one embodiment, the mRNA sequence is SEQ ID NO:6243, SEQ ID NO:8963, SEQ ID NO:8977 or SEQ ID NO:8978, wherein poly A is 90-110 adenosines. In one embodiment, the mRNA sequence is SEQ ID NO:6243, where poly A consists of 90-110 adenosines. In one embodiment, the mRNA sequence is SEQ ID NO:8963, where poly A consists of 90-110 adenosines. In one embodiment, the mRNA sequence is SEQ ID NO:8977, where poly A consists of 90-110 adenosines. In one embodiment, the mRNA sequence is SEQ ID NO:8978, where poly A consists of 90-110 adenosines. The present invention also protects compositions comprising the aforementioned mRNA encoding uricase and a delivery agent. In one embodiment, the delivery agent comprises lipid nanoparticles; the lipid nanoparticles include ionizable lipids, phospholipids, cholesterol, and PEG lipids. In one embodiment, the molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids in the lipid nanoparticles is 30-60:0-30:18.5-48.5:0-10. In one embodiment, the molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids in the lipid nanoparticles is 35-55:0-25:20-45:0.5-8. In one embodiment, the molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids in the lipid nanoparticles is 40-52:5-20:25-40:0.5-5. In one embodiment, the molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids in the lipid nanoparticles is 45-52:8-15:30-40:1-5. In one embodiment, the molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids in the lipid nanoparticles is 50:10:38.5:1.5. In one embodiment, the molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids in the lipid nanoparticles is 48.5:11.1:38.9:1.5. In one embodiment, the ionizable lipid is as shown in Formula II: Where n0 is an integer from 0 to 4; n1 is an integer from 2 to 7; n2 is an integer from 4 to 10; n3 is an integer from 2 to 8; n4 is an integer from 2 to 8; and n5 is an integer from 2 to 8. In one embodiment, n0 is 0, 1, 2, 3 or 4; preferably, n0 is 1, 2 or 3; more preferably, n0 is 1 or 2. In one embodiment, n1 is 2, 3, 4, 5, 6 or 7; preferably, n1 is 2, 3, 4 or 5; more preferably, n1 is 2, 3 or 4. In one embodiment, n2 is 4, 5, 6, 7, 8, 9 or 10; preferably, n2 is 6, 7, 8, 9 or 10; more preferably, n2 is 8, 9 or 10. In one embodiment, n3 is 2, 3, 4, 5, 6, 7 or 8; preferably, n3 is 3, 4, 5 or 6; more preferably, n3 is 4, 5 or 6. In one embodiment, n4 is 2, 3, 4, 5, 6, 7 or 8; preferably, n4 is 3, 4, 5 or 6; more preferably, n4 is 4, 5 or 6. In one embodiment, n5 is 2, 3, 4, 5, 6, 7 or 8; preferably, n5 is 3, 4, 5 or 6; more preferably, n5 is 4, 5 or 6. In one embodiment, the ionizable lipid is one or more combinations of SM102, MC3, DOTAP, ALC-0315, H1, H2, H3, H4, H5, H6, H7 or H8. Its structure is as follows: In one embodiment, the phospholipid is DSPC or DOPE; the PEG lipid has a molecular weight of PEG, PEG-modified compounds or mixtures thereof of 1000 Da to 20 kDa. In one embodiment, the mRNA in the composition is encapsulated in lipid nanoparticles. In one embodiment, the composition further includes pharmaceutically acceptable excipients. This invention also protects the use of the aforementioned mRNAs encoding different species of uricases or the aforementioned compositions in the preparation of preventive and / or therapeutic agents including but not limited to hyperuricemia and / or gout. In one embodiment, it may be used in combination with an immunosuppressant, if necessary. Immunosuppressants include, but are not limited to, one or more of methotrexate, azathioprine, rapamycin, prednisone, dexamethasone, cyclosporine, TGFβ, IL10, IDO1, TNF-α antibody, TSLP, HGF, VIP, RA, PGE2, or VEGF. In one embodiment, the immunosuppressant includes, but is not limited to, one or more of methotrexate, azathioprine, rapamycin, prednisone, dexamethasone, or cyclosporine. In one embodiment, the immunosuppressant is selected from one or more of methotrexate, azathioprine, rapamycin, or prednisone. In one embodiment, the immunosuppressant is selected from one or more of methotrexate, azathioprine, or rapamycin. In one embodiment, the immunosuppressant is methotrexate or azathioprine. In one embodiment, the immunosuppressant is azathioprine or rapamycin. In one embodiment, the immunosuppressant is rapamycin or prednisone. In one embodiment, the immunosuppressant is prednisone or dexamethasone. In one embodiment, the immunosuppressant is one or more proteins selected from TGFβ, IL10, IDO1, TNF-α antibody, TSLP, HGF, VIP, RA, PGE2, or VEGF. In one embodiment, the immunosuppressant is one or more proteins selected from TGFβ, IL10, IDO1, or TNF-α antibodies. In one embodiment, the immunosuppressant is TGFβ or IL10 protein. In one embodiment, the immunosuppressant is IL10 or IDO1 protein. In one embodiment, the immunosuppressant is IDO1 or TNF-α antibody protein. In one embodiment, the immunosuppressant is TGFβ or IDO1 protein. In one embodiment, the immunosuppressant is IL10 or TNF-α antibody protein. In one embodiment, the immunosuppressant is an mRNA expressing one or more proteins selected from TGFβ, IL10, IDO1, TNF-α antibody, TSLP, HGF, VIP, RA, PGE2, or VEGF. In one embodiment, the immunosuppressant is an mRNA expressing one or more proteins of TGFβ, IL10, IDO1, or TNF-α antibody. In one embodiment, the immunosuppressant is an mRNA expressing TGFβ or IL10 protein. In one embodiment, the immunosuppressant is an mRNA expressing IL10 or IDO1 protein. In one embodiment, the immunosuppressant is an mRNA expressing IDO1 or TNF-α antibody protein. In one embodiment, the immunosuppressant is an mRNA expressing TGFβ or IDO1 protein. In one embodiment, the immunosuppressant is an mRNA expressing the TGFβ protein. In one embodiment, the immunosuppressant is an mRNA expressing the IL10 protein. In one embodiment, the immunosuppressant is an mRNA expressing IDO1. In one embodiment, the immunosuppressant is an mRNA expressing TNF-α antibody protein. In one embodiment, the immunosuppressant is an mRNA expressing the TSLP protein. In one embodiment, the immunosuppressant is an mRNA expressing the HGF protein. In one embodiment, the immunosuppressant is an mRNA expressing the VIP protein. In one embodiment, the immunosuppressant is an mRNA expressing the RA protein. In one embodiment, the immunosuppressant is an mRNA expressing the PGE2 protein. In one embodiment, the immunosuppressant is an mRNA expressing the VEGF protein. The present invention also protects a method for preventing and / or treating hyperuricemia and / or gout by administering a therapeutically effective amount of the aforementioned mRNA encoding uricase or the aforementioned composition to a subject in need. In one embodiment, if necessary, immunosuppressants may be administered to the subjects in need simultaneously or in advance. Specifically, immunosuppressants may be administered 0-8 weeks in advance, depending on the specific circumstances. More preferably, immunosuppressants may be administered 0-6 weeks, 0-4 weeks, 0-2 weeks, 0-1 week, 0-5 days, 0-4 days, 0-3 days, 0-2 days, or 0-1 days in advance, depending on the specific circumstances. Compared with the prior art, the present invention has the following beneficial effects: This invention, through codon optimization and screening, obtains ORF sequences with high protein expression levels. Further screening using a combination of 5'UTR and 3'UTR yields multiple mRNAs with good uricase protein expression levels. Moreover, recombination and fusion of the ORF sequences significantly improve the expression efficiency and stability of the mRNAs. The mRNAs also exhibit excellent protein expression in animals. This indicates that the mRNAs provided by this invention can be expressed in animals to produce uricase, thereby oxidizing uric acid into allantoic acid, reducing uric acid levels, and thus preventing hyperuricemia and gout symptoms. Meanwhile, the mRNA prepared by this invention can maintain its effect for about 4-7 days after a single dose, eliminating the need for daily injections and improving patient compliance; and compared with recombinant protein, mRNA has a significant advantage in production cost. Detailed Implementation the term As used herein and unless otherwise stated, the term "alkyl" refers to a saturated carbon alkyl group consisting only of carbon and hydrogen atoms.

[0089] Straight-chain or branched hydrocarbon chain groups. In one embodiment, the alkyl group has, for example, 1 to 24 carbon atoms (C1-C2). 24 Alkyl groups, 4 to 20 carbon atoms (C4-C5) 20Alkyl groups, 6 to 16 carbon atoms (C6-C5) 16 Alkyl groups, 6 to 9 carbon atoms (C6-C9 alkyl groups), 1 to 15 carbon atoms (C1-C9 alkyl groups) 15 Alkyl groups, 1 to 12 carbon atoms (C1-C2) 12 Alkyl groups are alkyl groups with 1 to 8 carbon atoms (C1-C8 alkyl) or 1 to 6 carbon atoms (C1-C6 alkyl) and are connected to the rest of the molecule by a single bond. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (tert-butyl), 3-methylhexyl, 2-methylhexyl, etc. Unless otherwise stated, alkyl groups are optionally substituted. The term "lipid nanoparticle" or "LNP" refers to a particle having at least one nanometer (nm) scale size (e.g., 1 to 1000 nm) containing one or more types of lipid molecules. The LNPs described herein may further contain at least one non-lipid payload molecule (e.g., one or more nucleic acid molecules). In some embodiments, the LNP comprises a non-lipid payload molecule partially or completely encapsulated within a lipid shell. Specifically, in some embodiments, the payload is a negatively charged molecule (e.g., mRNA encoding a therapeutic protein), and the lipid component of the LNP contains at least one ionizable lipid. Without being bound by theory, it is anticipated that the ionizable lipid can interact with the negatively charged payload molecule and promote the incorporation and / or encapsulation of the payload into the LNP during LNF formation. Other lipids that can form a portion of the LNPs described herein include, but are not limited to, neutral and charged lipids, such as steroids, polymer-bound lipids, and various zwitterionic lipids. The term "ionizable lipid" refers to a lipid that carries a positive charge at any pH or hydrogen ion activity in its environment, or is capable of carrying a positive charge in response to the pH or hydrogen ion activity of its environment (e.g., the environment in which it is intended to be used). In some embodiments, the positive charge in an ionizable lipid is caused by the presence of a quaternary nitrogen atom. In some embodiments, an ionizable lipid comprises a zwitterionic lipid that carries a positive charge in its intended environment (e.g., at physiological pH). As used herein and unless otherwise stated, the term "pharmaceutically acceptable salt" includes both acid addition salts and base addition salts. As used herein and unless otherwise stated, the term "pharmaceutically acceptable carrier, diluent, or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, gliding agent, sweetener, diluent, preservative, dye / coloring agent, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier approved for acceptable use in humans or livestock. The term "composition" is intended to cover products containing a specified amount of a specified ingredient (e.g., the mRNA molecule provided herein) optionally selected. In some embodiments, the mRNA is a monocistronic mRNA containing only one ORF. In some embodiments, the monocistronic mRNA encodes a peptide or protein containing at least one epitope of a selected antigen (e.g., a pathogenic antigen or tumor-associated antigen). In other embodiments, the mRNA is a polycistronic mRNA containing two or more ORFs. In some embodiments, the polycistronic mRNA encodes two or more peptides or proteins that may be the same as or different from each other. In some embodiments, each peptide or protein encoded by the polycistronic mRNA contains at least one epitope of a selected antigen. In some embodiments, the different peptides or proteins encoded by the polycistronic mRNA each contain at least one epitope of a different antigen. In any of the embodiments described herein, the at least one epitope may be at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten epitopes of an antigen. The term "nucleobase" encompasses purines and pyrimidines, including the natural compounds adenine, thymine, guanine, cytosine, uracil, inosine, and their natural or synthetic analogues or derivatives. The term "administer / administration" refers to the act of injecting or otherwise physically delivering a substance present outside the body (such as the lipid nanoparticle composition described herein) into a patient's body, such as via mucosal, intradermal, intravenous, intramuscular delivery, and / or any other physical delivery method described herein or known in this art. When treating a disease, condition, illness, or its symptoms, the substance is usually administered after the onset of the disease, condition, illness, or its symptoms. When preventing a disease, condition, illness, or its symptoms, the substance is usually administered before the onset of the disease, condition, illness, or its symptoms. An "effective amount" is generally an amount sufficient to reduce the severity and / or frequency of symptoms; eliminate symptoms and / or underlying causes; prevent the occurrence of symptoms and / or their underlying causes; and / or improve or remedy damage caused by or associated with a disease, condition, or disorder, including, for example, infection and lesion formation. In some implementations, an effective amount is a therapeutic effective amount or a preventive effective amount. As used herein, the term "therapeuticly effective amount" refers to an amount of agent (e.g., a lipid nanoparticle composition as described herein) sufficient to reduce and / or improve the severity and / or duration of a given disease, condition, or disorder and / or its associated symptoms (e.g., infectious diseases such as those caused by viral infections, or proliferative disorders such as cancer). The "therapeuticly effective amount" of the substances / molecules / agents disclosed herein (e.g., lipid nanoparticle compositions as described herein) can vary depending on numerous factors, such as an individual's disease state, age, sex, and weight, and the ability of the substance / molecule / agent to elicit a desired response in the individual. A therapeutically effective amount includes the amount in which the therapeutically beneficial effect of the substance / molecule / agent outweighs any of its toxic or harmful effects. In some embodiments, the term "therapeuticly effective amount" refers to an amount of a lipid nanoparticle composition as described herein, or a therapeutic or preventative agent (e.g., therapeutic mRNA) contained therein, that is effective in treating a disease, condition, or disorder in a subject or mammal. The term "treatment" refers to the complete or partial relief of a symptom, disease, or ailment, or one or more symptoms associated with a symptom, disease, or ailment, or the slowing or stopping of the further progression or worsening of those symptoms, or the reduction or eradication of the cause of the symptom, disease, or ailment itself. The term "preventing" refers to reducing the likelihood of the onset (or recurrence) of a disease, condition, illness, or related symptoms. The term "side effect" encompasses undesirable and / or adverse effects of a therapy (such as a preventative or therapeutic agent). An undesirable effect is not necessarily an adverse effect. Adverse effects of a therapy (such as a preventative or therapeutic agent) may be harmful, unpleasant, or risky. Examples of side effects include diarrhea, cough, gastroenteritis, wheezing, nausea, vomiting, anorexia, abdominal cramps, fever, pain, weight loss, dehydration, hair loss, difficulty breathing, insomnia, dizziness, mucositis, neuromuscular effects, fatigue, dry mouth, loss of appetite, rash or swelling at the application site, flu-like symptoms such as fever, chills, and fatigue, digestive problems, and allergic reactions. Numerous other undesirable effects experienced by patients are known in this technology. The present invention will be further described in detail below with reference to specific embodiments. These embodiments are only used to explain the present invention and are not intended to limit the scope of the present invention. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the materials and reagents used are commercially available unless otherwise specified. The present invention will be further described in detail below with reference to specific embodiments. These embodiments are only used to explain the present invention and are not intended to limit the scope of the present invention. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the materials and reagents used are commercially available unless otherwise specified. Table 1 shows some of the sequences involved in this invention; Table 2 shows the sequences of divalent or trivalent uricase proteins or fusion proteins; Table 3 shows the amino acid sequences; Table 4 shows some mRNA sequences. Table 1 Sequence The sequences involved in expressing divalent or trivalent uricase proteins, or divalent or trivalent uricase fusion proteins, are any two or three sequences in SEQ ID NO:20-39 linked together by SEQ ID NO:40 and / or SEQ ID NO:41. Taking SEQ ID NO:20 as an example, the divalent sequence can be SEQ ID NO:2001-2032; or Uricase-R1 (SEQ ID NO:20) can be replaced with any one of SEQ ID NO:21-39, or the sequence after P2A or IRES can be replaced with any one of SEQ ID NO:20-39, which can form more ORF sequences involving divalent uricase proteins or divalent uricase fusion proteins. All of these are explicitly included in this application and will not be listed here due to space limitations. Table 2. Sequences involved in bivalent or trivalent uricase proteins or fusion proteins. Table 3 Amino acid sequences The amino acid sequences corresponding to Uricase-R1, Uricase-R2, Uricase-R3, and Uricase-R4 are SEQ ID NO:5001; the amino acid sequences corresponding to Uricase-R1-ABD, Uricase-R2-ABD, Uricase-R3-ABD, and Uricase-R4-ABD are SEQ ID NO:5002; the amino acid sequences corresponding to HSA-Uricase-R1, HSA-Uricase-R2, HSA-Uricase-R3, and HSA-Uricase-R4 are SEQ ID NO:5003; and the amino acid sequences corresponding to Uricase-R1-Fc, Uricase-R2-Fc, Uricase-R3-Fc, and Uricase-R4-Fc are SEQ ID NO:5004. The amino acid sequence corresponding to SEQ ID NO:37 is SEQ ID NO:62; the amino acid sequence corresponding to SEQ ID NO:38 is SEQ ID NO:63; and the amino acid sequence corresponding to SEQ ID NO:39 is SEQ ID NO:64. Taking SEQ ID NO:20 as an example, the mRNA sequences (monovalent uricase mRNA) that can be prepared are SEQ ID NO:65-124. Referring to the combination of SEQ ID NO:65-124, replacing the ORF sequence with SEQ ID NO:21-39, or the bivalent or trivalent ORF sequences listed in Table 2, or referring to the bivalent or trivalent ORF sequences formed by the replaceable sequences in Table 2, more mRNA sequences can be prepared. All of these are explicitly included in this application and are not listed here due to space limitations. Table 4. Partial mRNA sequences Example 1: Screening Sequence Since humans and some primates do not have endogenous uricase, the uricases used are all derived from other mammals and microorganisms. Therefore, uricases come from a variety of different species and have different amino acid sequences, but they can all play their role. The uricase involved in this application is derived from Aspergillus flavus (Rasburicase). Its amino acid sequence or the amino acid sequence of the fusion protein are SEQ ID NO:58-64, respectively. 1.1 Filtering UTR sequences The selected 5'UTR sequences are shown in SEQ ID NO:1-15, SEQ ID NO:42, and SEQ ID NO:44-50; the selected 3'UTR sequences are shown in SEQ ID NO:16-19, SEQ ID NO:43, and SEQ ID NO:51-57; taking one of the sequences in SEQ ID NO:20-39 as the ORF, it can be combined with different 5'UTR sequences and different 3'UTR sequences to obtain multiple sets of sequences. Taking SEQ ID NO:20 as an example, the ORF can be used to obtain SEQ ID NO:65-124 in Table 4. Sequences SEQ ID NO:65-124 and SEQ ID NO:260 were selected for testing, where the ORF of both sequences was sequence SEQ ID NO:20. The 5'UTR and 3'UTR sequences were different, and the effects of different 5'UTR and 3'UTR sequences were tested. The DNA sequences corresponding to the mRNAs of sequences SEQ ID NO:65-124 and SEQ ID NO:260 were synthesized by GenScript. The specific process is as follows: (1) Synthesize the DNA sequences corresponding to the mRNAs; (2) Construct the DNA sequences on the plasmid vector through homologous recombination; wherein the number of adenosines in poly A is 100±10. The plasmid vector containing the target gene was amplified and purified by E. coli, and then further linearized. After linearization, the plasmid was used to prepare capped mRNA using a one-pot method. For specific steps, please refer to patent 202210973168.5. The cap structure can be any one of compounds 1-54 listed in this invention. Specifically, the cap structure used in the mRNA of the following examples is compound 19. mRNA expression and enzyme activity detection in cells Transfection and expression: 293T cells were transfected with 0.6 × 10⁻⁶ cells. 6Cells were seeded at a density of [number] cells / mL in 6-well cell culture plates and cultured at 37°C with 5% CO2. The following day, mRNA was transfected into cells at a mass-to-volume ratio of 1:2 for mRNA to the transfection reagent jetMESSENGER, as follows: 200 μL jetMESSENGER Buffer was mixed with 4 μg mRNA, followed by 8 μL of transfection reagent. The mixture was incubated at room temperature for 15 min, then added to the cells and cultured at 37°C with 5% CO2. The medium was changed 6 h after transfection, and the supernatant was collected 24 h after transfection. Enzyme activity assay: Uricase activity in cell supernatant was measured using a uricase activity assay kit (BC4435). Sample processing and reaction solution preparation were performed according to the Solarbio uricase activity assay kit (BC4435) instructions. 30 μL of the processed sample and 170 μL of the corresponding reaction solution were transferred to a 96-well clear plate and incubated at 37°C for 30 min. The values ​​were measured at 505 nm using a spectrophotometer, and the uricase activity in the supernatant was calculated. UTR sequences and ORF sequences were screened using uricase activity detected by mRNA cell expression as an evaluation index. Table 5. mRNA expression results in cells. After screening, it was found that when the 5'UTR is SEQ ID NO:3 and the 3'UTR is SEQ ID NO:16; or when the 5'UTR is SEQ ID NO:42 and the 3'UTR is SEQ ID NO:43, that is, when the mRNA is SEQ ID NO:67 and SEQ ID NO:260, the expression level is higher than that of other sequences. 1.2 Screening of ORF sequences and fusion sequences The preparation, transfection, and expression of mRNA are described in section 1.1. The ORF sequences of the mRNA are SEQ ID NO: 20–39. Table 5. mRNA expression results in cells. After screening, it was found that when the 5'UTR is SEQ ID NO:3 and the 3'UTR is SEQ ID NO:16; or the 5'UTR is SEQ ID NO:42 and the 3'UTR is SEQ ID NO:43; and the ORF is SEQ ID NO:24 or SEQ ID NO:36, that is, when the mRNA is SEQ ID NO:157, SEQ ID NO:261, SEQ ID NO:247, or SEQ ID NO:262, the expression level is higher. Example 2 mRNA encapsulation and in vivo expression 2.1 mRNA encapsulation The main components of LNP include ionizable lipids, cholesterol, DSPC, and DMG-PEG2000, with molar ratios of 48.5%, 38.9%, 11.1%, and 1.5%, respectively, and a nitrogen-to-phosphorus ratio of 4.8 (i.e., the mass ratio of LNP to mRNA is 20:1). The ionizable lipids are selected from one or more combinations of SM102, MC3, DOTAP, ALC-0315, H1, H2, H3, H4, H5, H6, or H8. When the ionizable lipid is H7, the molar percentages of ionizable lipid, cholesterol, DSPC, and DMG-PEG2000 in LNP are 40%, 50.5%, 8.0%, and 1.5%, respectively, and the nitrogen-to-phosphorus ratio (N / P) is 6 (i.e., the mass ratio of LNP to mRNA is 16:1). When the ionizable lipid is one of SM102, MC3, DOTAP, ALC-0315, H1, H2, H3, H4, H5, H6 or H8, the molar proportions of ionizable lipid, cholesterol, DSPC and DMG-PEG2000 in LNP are 48.5%, 38.9%, 11.1% and 1.5%, respectively, and the nitrogen-phosphorus ratio is 4.8 (i.e., the mass ratio of LNP to mRNA is 20:1). 2.1.1 Lipid-ethanol solution: Dissolve the required ionizable lipids, cholesterol, DSPC and DMG-PEG2000 in anhydrous ethanol by molar ratio to prepare a lipid-ethanol solution with a total lipid concentration of 8 mM for later use. 2.1.2 mRNA-acetic acid buffer: Dilute the mRNA stock solution with acetate buffer (200mM, pH 5.0) to a suitable concentration and set aside. 2.1.3 Encapsulation: The mRNA-acetic acid buffer and lipid-ethanol solution were mixed at a flow rate ratio of 3:1 (buffer phase / ethanol phase), with a total flow rate of 3.6 mL / min, using a microfluidic system (syringe pump: SPM, Duko Industrial; mixing chip: LNP-B0, FluidicLab). The mixed sample was then dialyzed overnight at 4°C with 34 volumes of Tris salt buffer (20.5 mM, pH 7.5, containing 8.95% sucrose) (25 or 30 kDa MwCO) to obtain LNPs encapsulating mRNA. The mass ratio of LNPs to mRNA was approximately 5:1, 10:1, 15:1, and 20:1. To ensure accurate weighing of each component, the quantities and preparations could be scaled up proportionally. 2.2 In vivo expression of encapsulated mRNA (mRNA-LNP) mRNA-LNP (0.25 mg / kg) was injected into the tail vein of rats. Plasma samples were collected at 0, 3, 6, 24, 48, 72, 120, and 144 hours post-administration to detect plasma uricase activity. The tested mRNA sequences were SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:264, and SEQ ID NO:265. As shown in Figure 1, the plasma uricase activity in the treatment groups with mRNAs SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:264, and SEQ ID NO:265 was comparable, but significantly better than that in the treatment group with mRNA SEQ ID NO:260. Notably, the proteins expressed by SEQ ID NO:264 and SEQ ID NO:265 contain a (VPKEG) repeat peptide, but this did not significantly affect uricase activity. Example 3: In vivo efficacy evaluation of mRNA-LNP Experiment 1 The efficacy of mRNA-LNP was evaluated using UOX-KO transgenic mice (6-8 weeks old) lacking uricase as a model. mRNA-LNP was administered via tail vein injection at 0.5 mpk. Blood samples were collected at 6, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-administration to measure serum uric acid levels. A blank control group and a positive control group were also included. The positive control group received raburicase (2 mpk). The encapsulation of mRNA-LNP was as described in 2.1, the ionizable lipid was H8, and the mRNA sequence expressing uricase was SEQ ID NO:262. As shown in Figure 2, after tail vein injection of the prepared mRNA-LNP into mice, serum uric acid levels significantly decreased 6 hours after administration in the positive control group and returned to pre-administration levels after 24 hours, with the duration of effect after a single administration not exceeding 24 hours. In the mRNA-LNP group, serum uric acid levels significantly decreased 6 hours after administration, reaching their lowest level after 24 hours, and returned to pre-administration levels after 4-5 days. This indicates that mRNA-LNP exerts its effect in a more moderate manner and has a significantly longer duration of effect compared to the positive control group. Experiment 2 The experimental protocol was the same as in Experiment 1. Mice were divided into four groups: normal mice, negative control group, positive control group 1, positive control group 2, and test group. The normal mice group received no treatment. The negative control group received the formulation diluent, positive control group 1 received raburicase (2 mpk), and positive control group 2 received allopurinol. The formulation diluent and raburicase were administered once via tail vein injection, while allopurinol was dissolved at 200 μg / mL in drinking water and ingested freely. The encapsulation of mRNA-LNP was as described in 2.1, the ionizable lipid was H8, and the mRNA sequence of uricase expressed in the test group was SEQ ID NO:263. As shown in Figure 3, serum uric acid levels remained low in the normal mouse group; higher in the negative control group; significantly decreased in serum uric acid in positive control group 1 after 6 hours of administration, returning to pre-administration levels after 24 hours; reached its lowest level in positive control group 2 after 24 hours of administration, and then stabilized; in the test group, administration of mRNA-LNP resulted in a continuous decrease in serum uric acid, reaching its lowest level around day 5, after which the level began to rise slowly. Compared to positive control group 1, the test group showed a slower rate of uric acid reduction, but maintained this reduction for a longer period; the uric acid reduction levels in the test group and positive control group 2 were comparable within one week, but the initial rate of uric acid reduction in the test group was slightly slower than in positive control group 2. Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description and ideas, and it is neither necessary nor possible to exhaustively describe all implementation methods here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. An mRNA encoding uricase, characterized in that, The mRNA contains a coding region; the coding region contains one or more ORFs; the ORFs are selected from SEQ ID NO:20-39 or sequences that are at least 95% similar to one of SEQ ID NO:20-39.

2. The mRNA encoding uricase according to claim 1, characterized in that, The ORF is selected from one of SEQ ID NO:20-39 sequences with a similarity of at least 98%.

3. The mRNA encoding uricase according to claim 1, characterized in that, When the coding region contains at least two ORFs, the sequences of the ORFs may be the same or different; each ORF is separated by any one of the sequences in SEQ ID NO:40-41.

4. The mRNA encoding uricase according to claim 3, characterized in that, When the coding region contains at least three ORFs, the interval sequences may be the same or different.

5. The mRNA encoding uricase according to claim 3, characterized in that, When the coding region contains at least two ORFs, each ORF is selected from SEQ ID NO:20-39 or a sequence that has at least 98% similarity to one of SEQ ID NO:20-39.

6. The mRNA encoding uricase according to any one of claims 1-5, characterized in that, The ORF is one of the following: a1. The ORF is selected from SEQ ID NO:20-27, SEQ ID NO:36-39, or a sequence having at least 98% similarity to one of SEQ ID NO:20-27 or SEQ ID NO:36-39; a2. The ORF is selected from SEQ ID NO:20-27 and SEQ ID NO:36-39; a3. The ORF is selected from SEQ ID NO:24-27, SEQ ID NO:36-39, or a sequence having at least 98% similarity to one of SEQ ID NO:24-27 or SEQ ID NO:36-39; a4. The ORF is selected from SEQ ID NO:24-27 and SEQ ID NO:36-39; a5. The ORF is selected from SEQ ID NO:24, SEQ ID NO:36-39 or a sequence having at least 98% similarity to one of SEQ ID NO:24 or SEQ ID NO:36-39; a6. The ORF is selected from SEQ ID NO:36-39 or a sequence having at least 98% similarity to one of SEQ ID NO:36-39; a7. The ORF is selected from SEQ ID NO:36-39; a8. The ORF is selected from one of SEQ ID NO: 24, 36, 37, 38, 39; a9. The ORF is selected from one of SEQ ID NO: 36, 37, 38, 39; a10. The ORF is selected from one of SEQ ID NO: 36, 38, 39; a11. The ORF is one of SEQ ID NO:37, 38, 39.

7. The mRNA encoding uricase according to any one of claims 1 to 6, characterized in that, The mRNA also includes a 5'UTR, the sequence of which is selected from any one of SEQ ID NO:1-15 and SEQ ID NO:

42.

8. The mRNA encoding uricase according to any one of claims 1 to 7, characterized in that, The mRNA also includes a 3'UTR, the sequence of which is selected from any one of SEQ ID NO:16-19 and SEQ ID NO:

43.

9. The mRNA encoding uricase according to any one of claims 1 to 8, characterized in that, The mRNA also includes poly A, which contains at least 70 adenosine molecules.

10. An mRNA encoding uricase, characterized in that, The mRNA includes: (ii) 5'UTR; the 5'UTR is selected from any one of SEQ ID NO:1-15, SEQ ID NO:42; (iii) A coding region; the coding region contains one or more ORFs; the ORFs are selected from SEQ ID NO:20-39 or sequences that are at least 95% similar to one of SEQ ID NO:20-39; (iv) 3'UTR; the 3'UTR is selected from any one of SEQ ID NO:16-19 and SEQ ID NO:43; (v)poly A; the poly 3A contains at least 70 adenosines.

11. The mRNA encoding uricase according to claim 10, characterized in that, When the coding region contains at least two ORFs, the sequences of the ORFs may be the same or different; each ORF is separated by any one of the sequences in SEQ ID NO:40 or SEQ ID NO:

41.

12. The mRNA encoding uricase according to any one of claims 10 or 11, characterized in that, The ORF is one of the following situations: ： a1. The ORF is selected from SEQ ID NO:20-27, SEQ ID NO:36-39, or a sequence having at least 98% similarity to one of SEQ ID NO:20-27 or SEQ ID NO:36-39; a2. The ORF is selected from SEQ ID NO:20-27 and SEQ ID NO:36-39; a3. The ORF is selected from SEQ ID NO:24-27, SEQ ID NO:36-39, or a sequence having at least 98% similarity to one of SEQ ID NO:24-27 or SEQ ID NO:36-39; a4. The ORF is selected from SEQ ID NO:24-27 and SEQ ID NO:36-39; a5. The ORF is selected from SEQ ID NO:24, SEQ ID NO:36-39 or a sequence having at least 98% similarity to one of SEQ ID NO:24 or SEQ ID NO:36-39; a6. The ORF is selected from SEQ ID NO:36-39 or a sequence having at least 98% similarity to one of SEQ ID NO:36-39; a7. The ORF is selected from SEQ ID NO:36-39; a8. The ORF is selected from one of SEQ ID NO: 24, 36, 37, 38, 39; a9. The ORF is selected from one of SEQ ID NO: 36, 37, 38, 39; a10. The ORF is selected from one of SEQ ID NO: 36, 38, 39; a11. The ORF is one of SEQ ID NO:37, 38, 39.

13. The mRNA encoding uricase according to any one of claims 10 to 11, characterized in that, The poly A contains 70-140 adenosine, or 70-120 adenosine, or 80-120 adenosine, or 90-120 adenosine, or 90-110 adenosine, or 90-100 adenosine, or 100-140 adenosine, or 100-120 adenosine, or 100-110 adenosine.

14. The mRNA encoding uricase according to any one of claims 1 to 13, characterized in that, The sequences of the mRNA are SEQ ID NO:157, SEQ ID NO:247, and SEQ ID NO:261-265; Preferably, the mRNA sequence is SEQ ID NO:247, SEQ ID NO:261-265; Preferably, the sequence of the mRNA is SEQ ID NO:261-265; Preferably, the sequence of the mRNA is SEQ ID NO:247, SEQ ID NO:262-265; Preferably, the sequence of the mRNA is SEQ ID NO:262-265; Preferably, the sequence of the mRNA is SEQ ID NO:247 or SEQ ID NO:

262.

15. The mRNA encoding uricase according to any one of claims 1 to 14, characterized in that, The amino acid sequence encoded by the mRNA is one of the following: b1. The amino acid sequence encoded by the mRNA contains one of SEQ ID NO:58-64; b2. The amino acid sequence encoded by the mRNA contains one of SEQ ID NO: 59, 62-64; b3. The amino acid sequence encoded by the mRNA contains one of SEQ ID NO: 62-64; b4. The amino acid sequence encoded by the mRNA contains one of SEQ ID NO: 59, 62, 63; b5. The amino acid sequence encoded by the mRNA contains one of SEQ ID NO: 59, 62, 64; b6. The amino acid sequence encoded by the mRNA contains one of SEQ ID NO: 59, 63, 64.

16. The mRNA encoding uricase according to any one of claims 1 to 15, characterized in that, The mRNA also includes a 5' cap structure.

17. The mRNA encoding uricase according to claim 16, characterized in that, The 5' cap structure is selected from Cap0, Cap1, Cap2, or the structure shown in Formula I: Where R1 represents H and C 1-4 Alkyl, C 1-4 Halogenated alkyl, phenyl, C 1-4 Alkyl-substituted phenyl, halophenyl, benzyl, C 1-4 Alkyl-substituted benzyl or halobenzyl; R2 represents OH, halogen, or OC. 1-4 Alkyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Alkoxy-substituted C 1-4 Alkyl, C 1-4 Alkylamine substituent C 1-4 Alkyl, C 1-4 Amide group substituted C 1-4 Alkyl, benzyloxy, halobenzyloxy, benzyloxy-substituted C 1-4 Alkyl or halobenzyloxy-substituted C 1-4 alkyl; R3 and R4 are independently H and C. 1-4 Alkyl or C 1-4 Halogenated alkyl groups; R5 represents H and C. 1-4 Alkoxy, F, Cl, I, or N3; R6 represents H and C. 1-4 Alkyl, C 1-4 alkenyl, C 1-4 alkynyl, phenyl, C 1-4 Alkyl-substituted phenyl, halophenyl, benzyl, C 1-4 Alkyl-substituted benzyl or halobenzyl; B1 and B2 are each independently a base G, A, U or C, and substituted bases include, but are not limited to, 6-MeA, 5-MeU or 5-MeC.

18. The mRNA encoding uricase according to claim 17, characterized in that, R6 is H, C 1-4 Alkyl, C 1-4 alkenyl, C 1-4 Alkyne, phenyl, halophenyl, benzyl, or halobenzyl; Preferably, R6 is H or C. 1-4 Alkyl, phenyl, halophenyl, benzyl or halobenzyl.

19. The mRNA encoding uricase according to claim 17 or 18, characterized in that, R5 is H, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, F, Cl, I, or N3.

20. The mRNA encoding uricase according to any one of claims 17 to 19, characterized in that, R3 and R4 are any one of the following b1-b4: b1. R3 and R4 are each independently H, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, trifluoroethyl or trifluoroisopropyl; b2. R3 and R4 are each independently H, methyl, ethyl, isopropyl, trifluoromethyl, or trifluoroethyl; b3. R3 and R4 are each independently H, methyl, ethyl, or trifluoromethyl; b4. R3 and R4 are each independently H, methyl or trifluoromethyl.

21. The mRNA encoding uricase according to any one of claims 17 to 20, characterized in that, R2 is any one of the following c1-c4: c1. R2 is OH, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Alkoxy-substituted C 1-4 Alkyl, C 1-4 Alkylamine substituent C 1-4 Alkyl, C 1-4 Amide group substituted C 1-4 Alkyl, benzyloxy or benzyloxy-substituted C 1-4 alkyl; c2. The R2 is OH, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-3 Alkoxy-substituted C 1-3 Alkyl, C 1-3 Alkylamine substituent C 1-3 Alkyl, C 1-3 Amide group substituted C 1-3 Alkyl, benzyloxy or benzyloxy-substituted C 1-3 alkyl; c3. The R2 is OH, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-3 Alkoxy-substituted C 1-3 Alkyl, C 1-3 Alkylamine substituent C 1-3 Alkyl or C 1-3 Amide group substituted C 1-3 alkyl; c4. The R2 is OH, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkyl or C 1-3 Alkoxy-substituted C 1-3 alkyl.

22. The mRNA encoding uricase according to any one of claims 17 to 21, characterized in that, R1 is H, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoroisopropyl, phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 2,6-dimethyl-phenyl, 3,5-dimethyl-phenyl, 2-ethyl-phenyl, 3-ethyl-phenyl, 4-ethyl-phenyl, 2,6-diethyl-phenyl, 3,5-diethyl-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,6-chloro-phenyl, 3,5-chloro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-chloro-phenyl -Fluoro-phenyl, 2,6-fluoro-phenyl, 3,5-fluoro-phenyl, benzyl, 2-methyl-benzyl, 3-methyl-benzyl, 4-methyl-benzyl, 2,6-dimethyl-benzyl, 3,5-dimethyl-benzyl, 2-ethyl-benzyl, 3-ethyl-benzyl, 4-ethyl-benzyl, 2,6-diethyl-benzyl, 3,5-diethyl-benzyl, 2-chloro-benzyl, 3-chloro-benzyl, 4-chloro-benzyl, 2,6-chloro-benzyl, 3,5-chloro-benzyl, 2-fluoro-benzyl, 3-fluoro-benzyl, 4-fluoro-benzyl, 2,6-fluoro-benzyl or 3,5-fluoro-benzyl.

23. The mRNA encoding uricase according to claim 16, characterized in that, The 5' cap structure can be, but is not limited to, the following compounds:

24. The mRNA encoding uricase according to any one of claims 1 to 23, characterized in that, The mRNA contains at least one chemically modified nucleoside.

25. The mRNA encoding uricase according to claim 24, characterized in that, The chemically modified nucleoside is selected from pseudouracil, N1-methyl-pseudorazine, 1-ethylpseudorazine, 2-thiouracil, 4'-thiouracil, 5-methyluracil, or 5-methoxyuracil, or any combination thereof.

26. The mRNA encoding uricase according to claim 24 or 25, characterized in that, The percentage of chemically modified nucleosides in the mRNA is 10–100%, or 20–100%, or 30–100%, or 40–100%, or 50–100%, or 60–100%, or 70–100%, or 80–100%, or 90–100%, or 50–98%, or 50–95%, or 60–95%, or 70–95%, or 80–95%, or 90–95%, or 70–90%, or 80–90%.

27. A composition, characterized in that, It comprises the mRNA encoding nerve growth factor as described in any one of claims 1 to 26 and a delivery agent.

28. The composition according to claim 27, characterized in that, The delivery agent comprises lipid nanoparticles; the lipid nanoparticles contain ionizable lipids, phospholipids, cholesterol, and PEG lipids.

29. The composition according to claim 28, characterized in that, The molar ratio of ionizable lipids, phospholipids, cholesterol, and PEG lipids in the lipid nanoparticles is any one of the following c1-c4: c1. The molar ratio of ionizable lipids, phospholipids, cholesterol and PEG lipids is 30–60:0–30:18.5–48.5:0–10; The molar ratio of c2 ionizable lipids, phospholipids, cholesterol and PEG lipids is 35-55:0-25:20-45:0.5-8; The molar ratio of c3 ionizable lipids, phospholipids, cholesterol and PEG lipids is 40-52:5-20:25-40:0.5-5; The molar ratio of C4 ionizable lipids, phospholipids, cholesterol and PEG lipids is 45-52:8-15:30-40:1-5; The molar ratios of c5 ionizable lipids, phospholipids, cholesterol, and PEG lipids are 40:8.5:50.5:1.5, 50:10:38.5:1.5, or 48.5:11.1:38.9:1.

5.

30. The composition according to claim 28 or 29, characterized in that, The ionizable lipid is shown in Formula II: Where n0 is an integer from 0 to 4; n1 is an integer from 2 to 7; n2 is an integer from 4 to 10; n3 is an integer from 2 to 8; n4 is an integer from 2 to 8; n5 is an integer from 2 to 8. Alternatively, the ionizable lipids may be one or more combinations of SM102, MC3, DOTAP, ALC-0315, H1, H2, H3, H4, H5, H6, H7, or H8.

31. The composition according to any one of claims 28 to 30, characterized in that, The phospholipid is DSPC or DOPE; the PEG lipid has a molecular weight of PEG, PEG-modified compounds or mixtures thereof of 1000 Da to 20 kDa.

32. The composition according to any one of claims 27 to 31, characterized in that, The composition also includes pharmaceutically acceptable excipients.

33. The use of the mRNA encoding uricase according to any one of claims 1 to 26 or the composition according to any one of claims 27 to 32 in the preparation of a medicament for the prevention and / or treatment of hyperuricemia and / or gout.

34. The application according to claim 33, characterized in that, It can be used in combination with immunosuppressants.

35. The application according to claim 34, characterized in that, The immunosuppressants include, but are not limited to, one or more of the following: methotrexate, azathioprine, rapamycin, prednisone, dexamethasone, cyclosporine, TGFβ, IL10, IDO1, TNF-α antibody, TSLP, HGF, VIP, RA, PGE2, or VEGF.

36. A method for preventing and / or treating hyperuricemia and / or gout, characterized in that, Administer to a subject in need a therapeutically effective amount of the mRNA encoding uricase as described in any of claims 1 to 26 or the composition as described in any of claims 27 to 32.

37. The method for preventing and / or treating hyperuricemia and / or gout according to claim 36, characterized in that, Immunosuppressants were administered simultaneously or in advance to subjects who needed them.

38. The method for preventing and / or treating hyperuricemia and / or gout according to claim 37, characterized in that, The immunosuppressants include, but are not limited to, one or more of the following: methotrexate, azathioprine, rapamycin, prednisone, dexamethasone, cyclosporine, TGFβ, IL10, IDO1, TNF-α antibody, TSLP, HGF, VIP, RA, PGE2, or VEGF. Preferably, the TGFβ, IL10, IDO1, TNF-α antibody, TSLP, HGF, VIP, RA, PGE2, or VEGF can be proteins or mRNA expressing the proteins.

39. The method for preventing and / or treating hyperuricemia and / or gout according to claim 37 or 38, characterized in that, The immunosuppressants were administered to eligible subjects 0-8 weeks in advance.

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