Double-helix oligonucleotide construct comprising double-stranded miRNA and use thereof

Inventors

Lee, Taewoo • RYU, Jiwon • IM, Eun Ji

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Assignees

Bioneer Corp

Member
Bioneer
Bioneer

Bioneer is a biotechnology company specializing in molecular biology, offering solutions in nucleic acid synthesis, molecular diagnostics, protein production, and laboratory automation. The company's expertise covers oligonucleotide chemistry, gene synthesis, sample preparation, molecular diagnostics, and analytical services such as mass spectrometry and sequencing, serving clinical, research, and industrial sectors globally.

Publication Number

US-11820984-B2

Patent

Publication Date

2023-11-21

Expiration Date


Abstract

The present invention relates to a double-helix oligonucleotide construct comprising a double-stranded miRNA and a composition for preventing or treating cancer comprising the same. More particularly, the present invention relates to a double-helix oligonucleotide construct comprising miR-544a characterized by a method that effectively inhibits the proliferation of cancer cells or induces a voluntary death of cancer cells, and an anticancer composition comprising the construct.

Core Innovation

The disclosure describes a double-stranded oligonucleotide structure for inhibiting EGF signaling. The structure is defined by a structural formula (1) in which A is a hydrophilic compound, B is a hydrophobic compound, X and Y each represent a simple covalent bond or a linker-mediated covalent bond, and R represents miR-544a.

The structural concept is applied to a method for treatment of lung cancer by inhibiting EGF signaling through administration of the double-stranded oligonucleotide structure. The miR-544a is used as a double-stranded miRNA component within the A–X—R—Y—B architecture.

R is the miR-544a of the construct, with the miR-544a sequence being specified as SEQ ID NO:1 and SEQ ID NO:2 in the dependent claim set. Additional dependent claims further specify structural details by defining the nature of the X and Y bonds and narrowing the therapeutic effect toward inducing apoptosis in lung cancer cells.

Claims Coverage

The independent claim defines a treatment method for lung cancer that inhibits EGF signaling by administering a specifically structured double-stranded oligonucleotide. It includes four main inventive elements in the structural formula: a hydrophilic compound A, a hydrophobic compound B, covalent/linker connections X and Y, and miR-544a as R.

Treatment of lung cancer via EGF signaling inhibition

Administering a double-stranded oligonucleotide structure to treat lung cancer by inhibiting EGF signaling.

A–X—R—Y—B double-stranded oligonucleotide architecture

Using a double-stranded oligonucleotide structure having structural formula (1) where A is a hydrophilic compound, B is a hydrophobic compound, X and Y each independently represent a simple covalent bond or a linker-mediated covalent bond, and R represents miR-544a.

Hydrophilic compound A as a defined hydrophilic compound structure

Wherein A represents a hydrophilic compound selected as (P)n, (P_m-J), or (J-P_m)n with P as a hydrophilic monomer, n between 1 and 200, m between 1 and 15, and J as a linker.

Hydrophilic and hydrophobic molecular-weight constraints

Using a hydrophilic compound having a molecular weight in the range of 200 to 10,000 and using a hydrophobic compound having a molecular weight in the range of 250 to 1,000.

Bond degradation selection for X and Y

Wherein each covalent bond represented by X or Y is either non-degradable or degradable.

Apoptosis induction in lung cancer cells

Inducing apoptosis in lung cancer cells using the oligonucleotide to treat lung cancer.

Across the independent claim and its dependents, the inventive scope centers on administering a double-stranded A–X—R—Y—B oligonucleotide in which miR-544a is connected via covalent/linker bonds to hydrophilic and hydrophobic moieties, with additional limitations regarding defined hydrophilic structure, molecular-weight ranges, bond degradation properties, and an apoptosis-inducing therapeutic mechanism.

Stated Advantages

Inhibiting EGF signaling in lung cancer.

Treatment of lung cancer.

Inducing apoptosis in lung cancer cells.

Documented Applications

Method for treatment of lung cancer by inhibiting EGF signaling through administration of the double-stranded oligonucleotide structure (including apoptosis induction in lung cancer cells).

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