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Multi-target interfering nucleic acid molecule and application thereof

A nucleic acid interference and multi-target technology, which is applied in the field of multi-target interference nucleic acid molecules, can solve the problems that it is impossible to completely inhibit or reverse tumor growth, and achieve the effect of wide application prospects

Active Publication Date: 2014-08-27
BIOMICS BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Taking the treatment of tumors as an example, since tumors are a polygenic disease, its occurrence and development are complex biological processes involving multiple steps and factors. Therefore, the inhibition of a single oncogene cannot completely inhibit or reverse tumors. growth, single-target therapy has its limitations

Method used

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  • Multi-target interfering nucleic acid molecule and application thereof
  • Multi-target interfering nucleic acid molecule and application thereof
  • Multi-target interfering nucleic acid molecule and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Construction of multi-target interference nucleic acid molecules targeting Survivin gene and Bcl-2 gene

[0045] Survivin and Bcl-2 genes are widely and highly expressed in malignant tumor cells and inhibit tumor cell apoptosis. Studies have found that inhibiting the overexpressed Survivin or Bcl-2 gene in tumor cells and restoring their normal apoptotic pathway may be a new strategy for treating tumors. Therefore, the Survivin and Bcl-2 genes are selected as the target genes of the multi-target interfering nucleic acid molecule, which will be described as a specific embodiment.

[0046] siRNA targeting human Survivin gene is si-S:

[0047] Sense strand: 5'-GACUUGGCCCAGUGUUUUCUdTdT-3' (SEQ ID: 1)

[0048] Antisense strand: 5'-AGAAACACUGGGCCAAGUCdTdT-3' (SEQ ID: 2)

[0049] The sequence of siRNA targeting human Bcl-2 gene is si-B:

[0050] Sense strand: 5'-GGAUGACUGAGUACCUGAAdTdT-3' (SEQ ID: 3)

[0051] Antisense strand: 5'-UUCAGGUACUCAGUCAUCCdTdT-3' (SEQID: 4)

[...

Embodiment 2

[0063] An interfering nucleic acid molecule comprises a sense strand and two antisense strands, the 5' end of the antisense strand is targeted to the mRNA of the Bcl-2 gene, and the 3' end is targeted to the mRNA of the Survivin gene.

[0064] The sequence is as follows:

[0065] Sense strand: 5'-GACUUGGCCCAGUGUUUUCUACUGGAUGACUGAGUACCUGAA-3' (SEQ ID: 5)

[0066] Antisense strand: AGAAACACUGGGCCAAGUC (SEQ ID: 6)

[0067]UUCAGGUACUCAGUCAUCC (SEQ ID: 7)

[0068] Use the sequence SEQ ID: 5-7 to anneal into the interference nucleic acid double-stranded Sub-1, as follows:

[0069] (SEQ ID: 5)

[0070] 5'-GACUUGGCCCAGUGUUUCUACUGGAUGACUGAGUACCUGAA-3'

[0071] 3'-CUGAACCGGGUCACAAAGA CCUACUGACUCAUGGACUU-5'

[0072] (SEQ ID: 6) (SEQ ID: 7)

Embodiment 3

[0074] An interfering nucleic acid molecule comprises two sense strands and an antisense strand, the 5' end of the sense strand is targeted to the mRNA of the Survivin gene, and the 3' end is targeted to the mRNA of the Bcl-2 gene.

[0075] The Sub-2 structure is as follows:

[0076] Justice strand: GACUUGGCCCAGUGUUUCU (SEQ ID: 8)

[0077] GGAUGACUGAGUACCUGAA (SEQ ID: 9)

[0078] Antisense strand: 5'-UUCAGGUACUCAGUCAUCCAGUAGAAACACUGGGCCAAGUC-3'

[0079] (SEQ ID: 10)

[0080] Use the sequence SEQ ID: 8-10 to anneal into the interference nucleic acid double-stranded Sub-2, as follows:

[0081] (SEQ ID: 8) (SEQ ID: 9)

[0082] 5'-GACUUGGCCCAGUGUUUCU GGAUGACUGAGUACCUGAA-3'

[0083] 3'-CUGAACCGGGUCACAAAGAUGACCUACUGACUCAUGGACUU-5'

[0084] (SEQ ID: 10)

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Abstract

The invention relates to a multi-target interfering nucleic acid molecule and application thereof. The interfering nucleic acid molecule is composed of an antisense strand and a sense strand, the total length of the two strands is at least 30 nucleotides, and nucleotide incisions or gaps exist on the sense strand or the antisense strand or both the sense strand and the antisense strand. Any one strand of the interfering nucleic acid can target at least two target RNAs (Ribonucleic Acids), thereby interfering the translation process after transcription, and the interfering nucleic acid can not cause interferon reaction.

Description

technical field [0001] The present invention relates to multi-target interference nucleic acid molecules and applications thereof. Background technique [0002] RNA interference (RNA interference, RNAi) is a post-transcriptional gene silencing effect, which refers to the recognition of messenger RNA (messenger RNA, mRNA) with homologous sequences by exogenous or endogenous double-stranded RNA in organism cells ), which specifically cleaves it, thereby blocking its translation process. Compared with the traditional antisense oligonucleotide technology and ribozyme technology that inhibit gene expression, the effect of small interfering RNA (small interfering RNA, siRNA) silencing gene expression is tens to hundreds of times stronger, and it has been confirmed It has great potential in the treatment of various viral infectious diseases and tumors, and is an ideal therapeutic method for blocking gene expression. [0003] The mechanism by which RNAi exerts the effect of gene s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/113A61K48/00A61P35/00
Inventor 彭薇唐小军孙云成陆毅祥王晋康朱远源
Owner BIOMICS BIOTECH
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