Polyoligonucleic acid molecule and its application in multi-target interference

A technology for polynucleotides and oligonucleotides, applied to polyoligonucleotide molecules and their application in multi-target interference, can solve side effects, highly sensitive endonuclease and exonuclease, and cumbersome synthesis steps And other issues

Active Publication Date: 2018-07-31
GUANGZHOU RIBOBIO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, traditional RNAi reagents have the following deficiencies: 1) cumbersome synthesis steps and relatively high production costs; 2) highly sensitive to endonucleases and exonucleases, and low stability; 3) inhibition efficiency is not high enough to pre

Method used

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  • Polyoligonucleic acid molecule and its application in multi-target interference
  • Polyoligonucleic acid molecule and its application in multi-target interference
  • Polyoligonucleic acid molecule and its application in multi-target interference

Examples

Experimental program
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Example Embodiment

[0130] Example 1. Design and synthesis of polyoligonucleic acid molecules

[0131] 1. The design of polyoligonucleic acid molecules

[0132] The polynucleotide molecule of the present invention includes at least 3 oligonucleotide sequences. The size of each oligonucleotide sequence in the polynucleotide molecule is 15-50 nt, and each oligonucleotide sequence is from the 5'end. The 3'end consists of a targeted terminal segment TTS with a size of 5-24 nt, a targeted internal segment TIS with a size of 1-20 nt, and a linker terminal segment ATS with a size of 5-24 nt. Each oligonucleotide sequence in the polynucleotide molecule forms a double-stranded region with the other two sequences in the polynucleotide molecule except itself through sequence complementation, that is, the targeted terminal of each oligonucleotide The segment TTS is complementary to the adaptor terminal segment ATS of its adjacent oligonucleotide; and the targeting terminal segment TTS of each oligonucleotide is ...

Example Embodiment

[0143] Example 2. Application of polyoligonucleic acid molecules in inhibiting the expression of target genes in tumor cells

[0144] (1) Inhibition test against the same target gene

[0145] 1. Inhibition test of polyoligonucleic acid molecules with different sequence numbers

[0146] 1. Inhibition test of polyoligonucleic acid molecules targeting different sequence numbers of p65 gene

[0147] (1) Preparation of polyoligonucleic acid molecules

[0148] Three kinds of poly-oligonucleic acid N(R m1 +R m2 +R m3 ), namely 4(R12+R6+R12), 5(R12+R6+R12), 6(R12+R6+R12). Among them, N represents the number of sequences, m1 represents the number of nucleotides in the TTS fragment of each sequence, m2 represents the number of nucleotides in the TIS fragment of each sequence, and m3 represents the number of nucleotides in the ATS fragment of each sequence , Where each oligonucleotide sequence is RNA, the nucleotide sequence is shown in Table 1, and the target is mRNA. Among them, the sequence ...

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Abstract

The invention discloses a polyoligonucleic acid molecule and its application in multi-target interference. Through combination of a CON technology and a nanotechnology, the nucleic acid structure withan accurate and self-assembling capacity is constructed so that multi-target interference is realized. The polyoligonucleic acid molecule can be used for inhibiting expression of multiple genes in asignaling pathway of disease occurrence or development, or simultaneously inhibiting the expression of multiple disease target genes, and has broad application prospects in many fields such as biologyand chemistry. The experiment result shows that the polyoligonucleic acid molecule has the advantages of 1) high RNAi efficiency, 2) good chemical stability, strong anti-DNA enzyme degradation ability and long half-life, 3) low off-target rate, and 4) formation of nanoparticles with plasticity and strong cell introduction ability.

Description

technical field [0001] The invention belongs to the field of nucleic acid nanotechnology, and specifically relates to a polyoligonucleotide molecule and its application in multi-target interference. The molecule can efficiently regulate the expression of one or more target genes. Background technique [0002] CON (complementary oligonucleotide) technology enables artificially synthesized oligonucleotide molecules to bind to target molecules through sequence complementarity and change the biological characteristics of target molecules. CON technology includes two categories of RNAi (RNA interference) technology and ASO (antisense oligonucleotide) technology, which have been widely used in functional genomics research and are expected to become the third major treatment in addition to small molecule compounds and biological agents means. For example, mipomersen, which is used to treat homozygous familial hypercholesterolemia (FoFH), is a synthetic phosphorothioate oligonucleo...

Claims

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Application Information

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IPC IPC(8): C12N15/113C12N15/10A61K48/00A61P35/00
CPCA61K48/005C12N15/113C12N2310/14
Inventor 张必良杨秀群丹米其·萨玛斯基
Owner GUANGZHOU RIBOBIO
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