Nucleic acid construct comprising utr and use thereof
AssigneeShanghai Regenelead Therapies Co., Ltd.
InventorsJun Jiang, Linfeng Yang, Qinjun Chen, Xiaoyu Song, Wei Ning, Cheng Liao
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Abstract
The present invention relates to a nucleic acid construct comprising a UTR and use thereof. Specifically, the UTR can significantly improve the expression efficiency of a target gene in the nucleic acid construct. The nucleic acid construct may comprise a nucleic acid sequence expressing, for example, a human hepatocyte growth factor (hHGF), and can be used in a gene therapy for serious lower limb ischemia, diabetic foot, and other diseases.
Claims29
A nucleic acid construct, comprising:
- (a) an open reading frame (ORF), and
- (b) an untranslated region (UTR), the UTR comprising the following sequence:
- any one of SEQ ID NOs:
- 12 and 26 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 1 and 15 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 4-5 and 18-19 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 6-8 and 20-22 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 9-11 and 23-25 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 13 and 27 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 14 and 28 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 29 and 30 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 35-37 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 42 and 43 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 46 and 47 or a sequence having at least 90% identity thereto, or
- any one of SEQ ID NOs:
- 31-34, 38-41, and 44-45 or a sequence having at least 90% identity thereto.
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An RNA molecule, comprising:
- (a) an open reading frame (ORF), and
- (b) an untranslated region (UTR), the UTR comprising the following sequence:
- any one of SEQ ID NOs:
- 69 and 83 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 58 and 72 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 59-60 and 73-74 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 61-62 and 75-76 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 63-65 and 77-79 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 66-68 and 80-82 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 70 and 84 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 71 and 85 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 86 and 87 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 92-94 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 99 and 100 or a sequence having at least 90% identity thereto,
- any one of SEQ ID NOs:
- 103 and 104 or a sequence having at least 90% identity thereto, or
- any one of SEQ ID NOs:
- 88-91, 95-98, and 101-102 or a sequence having at least 90% identity thereto.
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An isolated polynucleotide, comprising (a) an open reading frame (ORF), the ORF comprising the sequence set forth in any one of SEQ ID NOs:
- 111-113 and 129-131 or a sequence having at least 90% identity thereto,
- wherein optionally, the polynucleotide comprises any one of the following (b)-(d) or any combination thereof:
- (b) a 5′UTR and/or a 3′UTR,
- (c) a poly-A tail, and
- (d) a 5′Cap;
- preferably, the poly-A tail is selected from the group consisting of A120, A30L70, HGH polyA, SV40 polyA, BGH polyA, rbGlob polyA, and SV40late polyA;
- more preferably, the poly-A tail is A120 or A30L70;
- preferably, the 5′Cap is selected from the group consisting of ARCA, 3′-O-Me-m7G(5′)ppp(5′)G, m7G(5′)ppp(5′)(2′OMeA)pU, m7Gppp(A2′O-MOE)pG, m7G(5′)ppp(5′)(2′OMeA)pG, m7G(5′)ppp(5′)(2′OMeG)pG, m7(3′OMeG)(5′)ppp(5′)(2′OMeG)pG, and m7(3′OMeG)(5′)ppp(5′)(2′OMeA)pG;
- preferably, the polynucleotide comprises one or more modifications selected from the group consisting of backbone modifications, sugar modifications, base modifications, and/or lipid modifications, wherein the base modifications are preferably pseudouridine modifications.
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Dependencies are inferred from the claim text.