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RNA interference preparation used for treating viral hepatitis B

A hairpin-type technology for hepatitis B virus, applied in antiviral agents, DNA/RNA fragments, viruses, etc.

Active Publication Date: 2013-10-02
厦门成朴希晟股权投资合伙企业(有限合伙)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has also been reported that due to the high mutation rate of HBV, inhibiting multiple sites of HBV can not only inhibit HBV more effectively, but also may prevent HBV gene mutation

Method used

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  • RNA interference preparation used for treating viral hepatitis B
  • RNA interference preparation used for treating viral hepatitis B
  • RNA interference preparation used for treating viral hepatitis B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] The segmented iNA includes antisense strands targeting two different HBV RNA loci. There are several non-complementary nucleotides in the middle of the continuous strand, for example:

[0084] iNA sequence number 231 (iNA ID#2and#8):

[0085] Sense strand: GGGUUUUUCUUGUUGACAAdTdTuauaCCGUGUGCACUUCGCUUCAdTdT

[0086] Antisense strand 1: UUGUCAACAAGAAAAACCCCG

[0087] Antisense strand 2: UGAAGCGAAGUGCACACGGUC

[0088] iNA ID#231A (segmented iNA designed according to iNA ID#2and#8iNA):

[0089] Sense strand: CCGUGUGCACUUCGCUUCAdTdTuauaGGGUUUUUCUUGUUGACAAdTdT

[0090] Ant i-sense strand1: UUGUCAACAAGAAAAACCCCG

[0091] Anti-sense strand2: U GAAGCGAAGU GCACACGGUC

[0092] iNA ID#232 (Segmented iNA designed according to iNA ID#2 and #5iNA)

[0093] Sense strand: GGGUUUUUCUUGUUGACAAdTdTuauaGGAUGUGUCUGCGGCGUUUUdTdT

[0094] Ant i-sense strand1: UUGUCAACAAGAAAAACCCCG

[0095] Ant i-sense strand2: AAACGCCGCAGACACAUCCAG

[0096] iNA ID#233 (segmented design according to i...

Embodiment 2

[0133] For ring or ring-like structures, each iNA is as follows. One strand consists of two polynucleotides in opposite directions (one 5' to 3' and the other 3' to 5'), where the 5'-3' direction is in the same order as the sequence of the target RNA. In solution, the polynucleotides at the two ends are hybridized together to form a circular structure. The other strand will be complementary to the single-stranded region of the loop and also to the target RNA. An example of such a sequence is as follows:

[0134] iNA ID#242 (circle-like HBV iNA designed according to iNA ID#2):

[0135] Justice Chain: GGGCCCGGGUUUUUCUUGUUGACAAUU CCCGGG (The underlined part is 3'-5' direction)

[0136] Antisense strand: UUGUCAACAAGAAAAACCCCG

[0137] iNA ID#243 (circle-like HBV iNA designed according to iNA ID#5):

[0138] Justice Chain: GGGCCCGGAUGUGUCUGCGGCGUUUUU CCCGGG (The underlined part is 3'-5' direction)

[0139] Antisense strand: AAACGCCGCAGACACAUCCAG

[0140] iNA ID#244 (quas...

Embodiment approach 3

[0156] Chemical modification:

[0157] iNA ID#249 (circle-like HBV iNA designed by iNA ID#2 and #8)

[0158] Sense strand: mGGGUUUUUCUUGUUGAmCAAdTdTuauamCCGmUGUGmCACUUCGCUUmCAdTdT

[0159] Antisense strand 1: UUGUCAACAAGAAAAACCCCG

[0160] Antisense strand 2: UGAAGCGAAGUGCACACGGUC

[0161] (bases before "m" refer to 2'-methoxy (2'-OMethyl) RNA bases. Bases before "d" refer to DNA bases)

[0162] iNA ID#250 (segmented design according to iNA ID#2 and #8iNA):

[0163] Sense strand: mGGGUUUUUCUUGUUGAmCAAdTdTuauamCCGmUGUGmCACUUCGCUUmCAdTdT

[0164] Antisense strand 1: UUGUmCAAmCAAGAAAAACCCCG

[0165] Antisense strand 2: UGAAGCGAAGUGCACACGGUC

[0166] (bases before "m" refer to 2'-methoxy (2'-O-Methyl) RNA bases. Bases before "d" refer to DNA bases)

[0167] iNA ID#250A (segmented design according to iNA ID#2 and #8iNA):

[0168] Sense strand: mCCGmUGUGmCACUUCGCUUmCAdTdTuauamGGGUUUUUCUUGUUGAmCAAdTdT

[0169] Antisense strand 1: UUGUmCAAmCAAGAAAAACCCCG

[0170] Antisense s...

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Abstract

The invention discloses a RNA interference preparation used for treating viral hepatitis B. The RNA interference preparation comprises one or more sense strands and one or more antisense strands, wherein one or more polynucleotide strands are complementary with one or more regions of HBV RNA. An iNA is an iNAs having a structure of double stands. The double strands have structures of linear, loop, similar-loop, hairpin-type, stem-loop, unidirectional or bidirectional. The RNA interference preparation provided by the invention can be used for treating viral hepatitis B.

Description

technical field [0001] The invention uses RNA interference (RNA interference, RNAi) to inhibit the replication of hepatitis B virus. Background technique [0002] Double-stranded RNA (dsRNA) inhibits the expression of proteins and silences genes, and has a wide range of potential uses in the treatment of human diseases. There are three ways for dsRNA to induce gene silencing: 1. Inactivation of transcriptional function, which refers to DNA or histone methylation under the guidance of RNA; 2. Small interfering nucleic acid (small interfering RNA, siRNA) induced messenger RNA ( mRNA) degradation; 3, the attenuation of RNA-mediated transcription function. But it is generally believed that dsRNA-induced gene interference (suppression) refers to the degradation of RNA in animal cells. Chemically synthesized small molecule RNA, such as siRNA, can degrade more than 95% of mRNA in cells under submicromolar concentration under enzymatic catalysis. [0003] The effect of RNAi can l...

Claims

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Application Information

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IPC IPC(8): C12N15/113A61K48/00A61P31/20A61P1/16
CPCA61K31/713A61P1/16A61P31/12A61P31/20C12N15/1131C12N2310/14C12N2730/10122
Inventor 崔坤元梁东
Owner 厦门成朴希晟股权投资合伙企业(有限合伙)
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