WO2025201286A1 - Utr pour favoriser la traduction d'arn - Google Patents

Utr pour favoriser la traduction d'arn

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Publication number
WO2025201286A1
WO2025201286A1 PCT/CN2025/084581 CN2025084581W WO2025201286A1 WO 2025201286 A1 WO2025201286 A1 WO 2025201286A1 CN 2025084581 W CN2025084581 W CN 2025084581W WO 2025201286 A1 WO2025201286 A1 WO 2025201286A1
Authority
WO
WIPO (PCT)
Prior art keywords
utr
sequence
rna molecule
polypeptide
rna
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2025/084581
Other languages
English (en)
Chinese (zh)
Other versions
WO2025201286A9 (fr
Inventor
杨雪瑞
吕瑶
张小驹
刘安东
王利娜
吴鼎
叶子惠
于奕凡
毛沁心
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tsinghua University
Hangzhou Jitai Pharmaceutical Technology Co Ltd
Beijing Jitai Pharmaceutical Technology Co Ltd
Original Assignee
Tsinghua University
Hangzhou Jitai Pharmaceutical Technology Co Ltd
Beijing Jitai Pharmaceutical Technology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tsinghua University, Hangzhou Jitai Pharmaceutical Technology Co Ltd, Beijing Jitai Pharmaceutical Technology Co Ltd filed Critical Tsinghua University
Publication of WO2025201286A1 publication Critical patent/WO2025201286A1/fr
Publication of WO2025201286A9 publication Critical patent/WO2025201286A9/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/67—General methods for enhancing the expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Definitions

  • the present invention relates to the field of biomedicine, in particular to the field of RNA drugs. Specifically, the present invention relates to UTRs that promote RNA translation obtained using artificial intelligence technology, as well as RNA molecules containing the UTRs and their uses.
  • RNA such as mRNA or circular RNA
  • RNA drug molecules
  • RNA such as mRNA or circular RNA
  • RNA can also provide immediate and controllable protein expression, making it an ideal choice for treating diseases caused by specific gene deletions.
  • RNA such as mRNA or circular RNA
  • the untranslated region (UTR) of mRNA plays a crucial regulatory role in mRNA expression.
  • Different UTR sequences can directly influence the expression level of the mRNA-encoded protein by affecting mRNA stability and translation efficiency. Therefore, optimizing and screening 5' UTR sequences to increase the expression level of the mRNA-encoded protein is crucial for enhancing therapeutic efficacy and activating vaccine immune responses.
  • the present invention relates to a 5'UTR (5' untranslated region), which comprises a nucleotide sequence or its complementary sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with one of SEQ ID NOs: 1-13 and 41-60.
  • the 5'UTR comprises the nucleotide sequence shown in one of SEQ ID NOs: 1-13 and 41-60, or its complementary sequence.
  • the 5'UTR comprises the nucleotide sequence shown in one of SEQ ID NOs: 1, 3-5, 7-11, 13, 41-46, 48, 50-53, 55-57, 59-60, or its complementary sequence. More preferably, the 5'UTR comprises the nucleotide sequence shown in one of SEQ ID NOs: 4-5, 7-10, 41, 43-45, 48, 50-51, 53, 55, 57, 59, or its complementary sequence.
  • the present invention relates to a 3'UTR (3' untranslated region)
  • the 3'UTR comprises a nucleotide sequence as shown in one of SEQ ID NOs: 15-28 and 61-80, or a complementary sequence thereof, more preferably, the 3'UTR comprises a nucleotide sequence as shown in one of SEQ ID NOs: 15-20, 22-23, 25-26, 28, 61-71, 73-80, or a complementary sequence thereof, more preferably, the 3'UTR comprises a nucleotide sequence as shown in one of SEQ ID NOs: 15-16, 18-19, 22, 25, 28, 61, 63-66, 68, 70-71, 73-80, or a complementary sequence thereof; or
  • ii) comprising a nucleotide sequence shown in one of SEQ ID NOs: 15-28 and 61-80 or its complementary sequence with one or more additional sequences inserted, preferably the additional sequence is a miRNA binding site, more preferably the additional sequence is selected from the full-length microRNA reverse complementary sequence or the reverse complementary sequence of its seed sequence, more preferably the full-length microRNA reverse complementary sequence is 19-25 nt in length or the reverse complementary sequence of the seed sequence is 7-8 nt in length.
  • the present invention relates to an RNA molecule for expressing a polypeptide of interest, comprising a 5'UTR of the present invention and/or a 3'UTR of the present invention.
  • the present invention relates to a nucleic acid vector comprising a coding sequence for the RNA molecule of the present invention.
  • the invention in another aspect, relates to a cell comprising the RNA molecule of the invention or the nucleic acid vector of the invention.
  • the present invention relates to a method for increasing the expression of a polypeptide of interest in a cell, the method comprising introducing into the cell an RNA molecule of the present invention and/or a nucleic acid vector of the present invention.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising the RNA molecule of the present invention, and/or the nucleic acid vector of the present invention and/or the host cell of the present invention, and a pharmaceutically acceptable carrier.
  • the present invention relates to the use of the 5'UTR of the present invention and/or the 3'UTR of the present invention for improving the translation efficiency of a polypeptide of interest in an RNA molecule comprising the coding sequence of the polypeptide of interest.
  • FIG. 1 Exemplary mRNA sequences containing UTRs of the present invention.
  • Figure 3 Relative light units of firefly luciferase in lysates from cells transfected with mRNA containing candidate 5’ UTRs. Statistical differences were determined using a student’s t-test.
  • Figure 6 Flow cytometry analysis of the relative intensity of red fluorescent protein in cells transfected with mRNA containing candidate 3’UTRs.
  • FIG7 Fluorescence quantitative analysis of the relative intensity of green fluorescent protein after transfection of 293T cells with mRNA containing the 3′UTR of the present invention with three microRNA binding sites, and its changing trend within 24 hours.
  • FIG8 Fluorescence quantitative analysis of the relative intensity of green fluorescent protein after transfection of Hela cells with mRNA containing the 3′UTR of the present invention containing three microRNA binding sites, and its changing trend within 24 hours.
  • the term “and/or” encompasses all combinations of items connected by the term, and should be treated as if each combination had been individually listed herein.
  • “A and/or B” encompasses “A,” “A and B,” and “B.”
  • “A, B, and/or C” encompasses “A,” “B,” “C,” “A and B,” “A and C,” “B and C,” and “A and B and C.”
  • Nucleotides are referred to by their single-letter designations as follows: “A” for adenosine or deoxyadenosine (RNA or DNA, respectively), “C” for cytidine or deoxycytidine, “G” for guanosine or deoxyguanosine, “U” for uridine, “T” for deoxythymidine, “R” for purine (A or G), “Y” for pyrimidine (C or T), “K” for G or T, “H” for A or C or T, “I” for inosine, and “N” for any nucleotide.
  • nucleotide sequences herein may be presented as DNA sequences (including T), when reference is made to RNA, one skilled in the art can readily determine the corresponding RNA sequence (i.e., replacing T with U).
  • Polypeptide “peptide,” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residues is an artificial chemical analog of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers.
  • the terms “polypeptide,” “peptide,” “amino acid sequence,” and “protein” may also include modified forms including, but not limited to, glycosylation, lipid attachment, sulfation, gamma-carboxylation of glutamic acid residues, hydroxylation, and ADP-ribosylation.
  • the protein or nucleic acid may be composed of the sequence, or may have additional amino acids or nucleotides at one or both ends of the protein or nucleic acid, but still have the activity described in the present invention.
  • the present invention relates to a 5’UTR (5’ untranslated region) comprising a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity to one of SEQ ID NOs: 1-13 and 41-60, or its complementary sequence.
  • the 5’UTR comprises the nucleotide sequence shown in one of SEQ ID NOs: 1-13 and 41-60, or its complementary sequence.
  • the 5’UTR comprises the nucleotide sequence shown in one of SEQ ID NOs: 1, 3-5, 7-11, 13, 41-46, 48, 50-53, 55-57, 59-60, or its complementary sequence. In some more preferred embodiments, the 5’UTR comprises a nucleotide sequence shown in one of SEQ ID NO: 4-5, 7-10, 41, 43-45, 48, 50-51, 53, 55, 57, 59 or its complementary sequence.
  • the 5'UTR is a non-natural 5'UTR. In some embodiments, the 5'UTR is an artificial intelligence designed 5'UTR.
  • 3'UTR refers to the sequence between the stop codon and the poly(A) sequence of a polypeptide-coding sequence in an mRNA.
  • the 3'UTR can regulate mRNA translation by interacting with mRNA-binding proteins, miRNAs, and other proteins.
  • the sequence and structural features of the 3'UTR can influence mRNA stability, ribosome scanning, and the formation of the translation termination complex, thereby affecting protein expression levels.
  • the 3'UTR of the present invention has a certain degree of stability and can tolerate a certain degree of sequence insertion (such as a microRNA binding site) without affecting its ability to promote translation of the coding region in the mRNA molecule or affecting the stability of the mRNA molecule. Therefore, in some embodiments, the 3'UTR of the present invention further has one or more (e.g., 1-5) additional sequences inserted.
  • the additional sequence is a miRNA binding site. In some preferred embodiments, the additional sequence is selected from the reverse complementary sequence of the full-length microRNA or the reverse complementary sequence of the seed sequence of the microRNA. In some preferred embodiments, the reverse complementary sequence of the full-length microRNA is 19-25 nt in length or more preferably the reverse complementary sequence of the seed sequence of the microRNA is 7-8 nt in length.
  • the 3'UTR is a non-natural 3'UTR. In some embodiments, the 3'UTR is an artificial intelligence designed 3'UTR.
  • the present invention provides an RNA molecule comprising a 5'UTR of the present invention and/or a 3'UTR of the present invention.
  • the RNA molecule comprises a 3'UTR of the present invention.
  • the 3'UTR of the present invention can be combined with different 5'UTRs to achieve the effect of enhancing the translation of the RNA molecule.
  • the 5'UTR can be a 5'UTR known in the art, such as a 5'UTR from a natural RNA molecule, or a non-natural 5'UTR, such as a 5'UTR designed by artificial intelligence.
  • the RNA molecule comprises a 5'UTR of the present invention and a 3'UTR of the present invention.
  • the 5'UTR of the present invention can be combined with the 3'UTR of the present invention to achieve an effect of enhancing the translation of the RNA molecule.
  • the RNA molecule is a messenger RNA (mRNA).
  • mRNA messenger RNA
  • An mRNA molecule is typically a linear RNA molecule.
  • the RNA molecule is a circular RNA molecule.
  • a circular RNA molecule is a covalently closed RNA molecule.
  • the RNA molecule is used to express a polypeptide of interest in a cell.
  • the RNA molecule comprises a coding sequence for a polypeptide of interest, operably linked to the 5' UTR and/or the 3' UTR. Operably linked means that a given element is capable of effectively regulating translation of the polypeptide of interest from the RNA molecule in a cell.
  • the RNA molecule further comprises a poly(A) sequence.
  • the poly(A) sequence is operably linked to a coding sequence for a polypeptide of interest.
  • Poly(A) sequences typically contain multiple adenine nucleotides.
  • the addition of poly(A) sequences contributes to the stability and transport of mRNA, prevents its degradation, and plays an important role in post-transcriptional modification.
  • the poly(A) sequence can be a continuous chain of pure adenine nucleotides, but it can also be a variant containing non-adenine nucleotides, as long as its function is equivalent to that of a conventional poly(A) sequence, that is, it can provide similar biological functions as the natural poly(A) sequence, such as affecting mRNA stability, translation efficiency, or ribosome binding.
  • the poly (A) sequence comprises about 20 to about 500 consecutive adenine nucleotides (A), for example, about 25, about 50, about 100, about 150, about 175, about 200, about 300, about 400, about 500 consecutive adenine nucleotides (A).
  • the RNA molecule comprises the following sequence from 5' to 3' direction:
  • the RNA molecule comprises the following sequence from 5' to 3' direction:
  • the 5'UTR described in 1] can be a 5'UTR known in the art, such as a 5'UTR from a natural RNA molecule, or can be non-natural, such as a 5'UTR designed by artificial intelligence. In some embodiments, the 5'UTR is a 5'UTR of the present invention.
  • polypeptide of interest can be any polypeptide to be expressed in a target cell.
  • the polypeptide of interest may be a polypeptide of eukaryotic, prokaryotic, or viral origin.
  • the polypeptide of interest may be any polypeptide for therapeutic, prophylactic, or diagnostic purposes.
  • the polypeptide of interest may be an antigen, an antibody, a gene editing enzyme such as a CRISPR nuclease, etc.
  • the polypeptide of interest may also be a chimeric antigen receptor, an immunomodulatory protein, a transcription factor, etc. Examples of such polypeptides include, but are not limited to, luciferase, red/green fluorescent protein, human erythropoietin, and ⁇ -galactosidase.
  • Codon optimization refers to a method for modifying a nucleic acid sequence to enhance expression in a host cell of interest by replacing at least one codon (e.g., about or more than about 1, 2, 3, 4, 5, 10, 15, 20, 25, 50 or more codons) of a native sequence with a codon that is more frequently or most frequently used in the genes of a host cell.
  • codon e.g., about or more than about 1, 2, 3, 4, 5, 10, 15, 20, 25, 50 or more codons
  • Codon preference (the difference in codon usage between organisms) is often associated with the translation efficiency of mRNA, and this translation efficiency is considered to depend on the properties of the codons translated and the availability of specific transfer RNA (tRNA) molecules.
  • tRNA transfer RNA
  • genes can be customized to optimal gene expression based on codon optimization in a given organism. Codon utilization tables can be easily obtained. See, Nakamura Y. et al., “Codon usage tabulated from the international DNA sequence databases: status for the year 2000. Nucl. Acids Res., 28:292 (2000).
  • the RNA molecule is chemically synthesized. In some embodiments, the RNA molecule is obtained by in vitro transcription.
  • the “5’ cap” for RNA includes the 5’ cap structure present on natural mRNA and its analogs.
  • the 5’ cap structure on natural mRNA refers to the methylated guanylate connected to the 5’ terminal nucleotide of RNA via pyrophosphate to form a 5’,5’-triphosphate linkage (5’,5’-triphosphate linkage).
  • There are usually three types of 5’ caps m7G5’ppp5’Np, m7G5’ppp5’NmpNp, m7G5’ppp5’NmpNmpNp), which are called Cap0, Cap1 and Cap2 respectively.
  • an RNA molecule comprising a 5'UTR of the invention results in comparable expression or increased expression of the polypeptide of interest in a cell (e.g., in HEK293T or HCT116 cells) compared to a corresponding RNA molecule comprising a control 5'UTR (e.g., SEQ ID NO: 14), preferably, expression of the polypeptide of interest is increased by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 100% or more.
  • Preferred 5'UTRs of the invention result in an increase in expression of the polypeptide of interest of at least 20%. More preferred 5'UTRs of the invention result in an increase in expression of the polypeptide of interest of at least 50%.
  • an RNA molecule comprising a 3'UTR of the present invention results in comparable expression or increased expression of the polypeptide of interest in a cell (e.g., in HEK293T or HCT116 cells) compared to a corresponding RNA molecule comprising a control 3'UTR (e.g., SEQ ID NO: 29).
  • expression of the polypeptide of interest is increased by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 100% or more.
  • Preferred 3'UTRs of the present invention result in an increase in expression of the polypeptide of interest of at least 20%. More preferred 3'UTRs of the present invention result in an increase in expression of the polypeptide of interest of at least 50%.
  • linear DNA fragments e.g., PCR products, linear plasmid fragments), plasmid vectors, viral vectors, cosmids, bacterial artificial chromosomes (BACs), yeast artificial chromosomes (YACs), etc.
  • the pharmaceutical composition is used to treat and/or prevent a disease in a subject.
  • the specific disease to be treated and/or prevented depends on the polypeptide of interest.
  • the pharmaceutical composition can be a vaccine.
  • a nucleic acid fragment containing a T7 promoter, a candidate 5'UTR or a control 5'UTR, a sequence encoding firefly luciferase or red fluorescent protein (Table 3), a 3'UTR (SEQ ID NO: 29), a poly(A) sequence containing 100 A nucleotide residues, and a type IIS restriction endonuclease cleavage site was synthesized in vitro and cloned into an in vitro transcription vector (pIVTRup, Addgene plasmid #101362).
  • the control 5'UTR sequence element (SEQ ID NO: 14) was derived from the Moderna mRNA1273 expression vector, complete sequence (GenBank: OR134578.1).
  • the 3'UTR sequence element (SEQ ID NO: 29) was derived from the Moderna mRNA1273 expression vector, complete sequence (GenBank: OR134578.1).
  • Example 2 The vector obtained in Example 2 was linearized and transcribed in vitro using T7 RNA polymerase to produce mRNA molecules, while simultaneously adding a 5'-cap structure.
  • the 5'-cap structure is incorporated into the transcript as the first nucleotide during in vitro transcription via co-transcriptional capping, directly producing mRNA molecules with the Cap1 structure.
  • Figure 1 shows the sequence of an exemplary mRNA containing a candidate UTR element of the present invention.
  • Luciferase chemiluminescence absorbance assay for determining translation efficiency
  • Luciferase activity was measured as relative light units (RLU) in a multiwell plate reader (Agilent). Luciferase activity was measured sequentially from individual samples in the luciferase assay. 20 ⁇ l of lysate was pipetted, 50 ⁇ l of buffer containing firefly luciferase substrate was added, the plate was shaken to mix, and the absorbance was measured.
  • RLU relative light units
  • the candidate 5'UTR of the present invention can achieve comparable or better translation efficiency than the control 5'UTR.
  • RNA molecules containing candidate 3'UTR sequence elements encoding the protein sequence of firefly luciferase
  • Luciferase activity was measured as relative light units (RLU) in a multiwell plate reader (Agilent). Luciferase activity was measured sequentially from individual samples in the luciferase assay. 20 ⁇ l of lysate was pipetted, 50 ⁇ l of buffer containing firefly luciferase substrate was added, the plate was shaken to mix, and the absorbance was measured.
  • RLU relative light units
  • 293T human embryonic kidney cells were seeded in 24-well plates at a density of 2 ⁇ 10 5 cells/well. The next day, the cells were washed in Opti-MEM and subsequently transfected with 200 ng/well of Lipofectamine 2000-complexed mRNA encoding red fluorescent protein containing candidate UTR sequence elements in Opti-MEM, and co-transfected with an equal amount of green fluorescent protein mRNA (SEQ ID NO: 35) as an internal control. 6 hours after transfection, the mixed culture medium was aspirated and replaced with complete culture medium. 24 hours after transfection, the culture medium was aspirated, trypsin was added for digestion for 3 minutes, neutralized and the cell samples were collected. Cells were analyzed in a flow cytometer using PBS as a suspension, and the intensity of red and green fluorescence was read.
  • the candidate 3'UTR of the present invention can achieve comparable or better translation efficiency than the control 3'UTR.
  • RISC RNA-induced silencing complex
  • additional complementary pairs between miRNA sequences and mRNAs can enhance miRNA-mediated gene regulation.
  • This additional complementary pairing typically occurs in regions outside the miRNA seed sequence. Matching in these regions can increase the affinity of the miRNA for its target, thereby enhancing the efficiency of mRNA repression.
  • Moderna uses a strategy of inserting the full-length reverse complement sequence of a miRNA into the 3'UTR region. This design enables the miRNA to form a more extensive complementary pairing with its target mRNA, not just with the seed sequence, thereby enhancing the regulatory efficacy of the miRNA on the mRNA.
  • This relative intensity can indicate the translational regulatory capacity of the 3'UTR sequence, and changes in fluorescence intensity over 24 hours can indicate the effect of the 3'UTR sequence on mRNA stability.
  • sequence of the new 3'UTR obtained by inserting the reverse complementary sequence of the full-length hsa-microRNA-122-5p into three random sites in 3'UTR-seq24 is as follows (SEQ ID NO: 38):
  • sequence of the mRNA containing 1-hour degraded green fluorescent protein and a new 3'UTR sequence obtained by inserting the reverse complementary sequence of the full-length hsa-microRNA-122-5p into three random sites in 3'UTR-seq24 is as follows (SEQ ID NO: 40):

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Abstract

La présente invention concerne le domaine de la biomédecine, et concerne en particulier le domaine des médicaments à ARN. Plus particulièrement, la présente invention concerne une UTR pour favoriser la traduction d'ARN, laquelle UTR est obtenue au moyen d'une technologie d'intelligence artificielle, et une molécule d'ARN contenant l'UTR et son utilisation.
PCT/CN2025/084581 2024-03-26 2025-03-25 Utr pour favoriser la traduction d'arn Pending WO2025201286A1 (fr)

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Application Number Priority Date Filing Date Title
CN202410354702.3 2024-03-26
CN202410354542 2024-03-26
CN202410354702 2024-03-26
CN202410354542.2 2024-03-26

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WO2025201286A1 true WO2025201286A1 (fr) 2025-10-02
WO2025201286A9 WO2025201286A9 (fr) 2026-01-15

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