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Double stranded oligonucleotide construct comprising androgen receptor specific sequence, and composition for preventing hair loss and promoting hair growth comprising same

A technology of androgen receptor and oligonucleotide, which is applied in the direction of medical preparations containing active ingredients, drug combinations, medical preparations with non-active ingredients, etc., and can solve problems such as hair growth products that have not yet been developed

Pending Publication Date: 2021-08-17
BIONEER
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the hair loss prevention agents developed so far target DHT and 5-α-reductase, and no agent or hair growth product targeting the androgen receptor directly related to androgen has been developed

Method used

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  • Double stranded oligonucleotide construct comprising androgen receptor specific sequence, and composition for preventing hair loss and promoting hair growth comprising same
  • Double stranded oligonucleotide construct comprising androgen receptor specific sequence, and composition for preventing hair loss and promoting hair growth comprising same
  • Double stranded oligonucleotide construct comprising androgen receptor specific sequence, and composition for preventing hair loss and promoting hair growth comprising same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0133] Example 1. Algorithm and Candidate Sequence Selection for Oligonucleotide Screening Targeting the Androgen Receptor

[0134] The siRNA-based high-throughput drug screening method is capable of generating all possible candidate sequences by applying a 1-base or 2-base sliding window algorithm to total mRNA, and is also capable of removing unnecessary candidate sequences by homology filtering, thereby Confirm the degree of inhibition of gene expression for all final selected oligonucleotides.

[0135] First, based on the exon map of human androgen receptor mRNA NM_000044.3 (isoform 1, 10,661bp) and NM_001011645.2 (isoform 2, 8112bp), the isotype consensus region was extracted for androgen receptor mRNA. The design process of oligonucleotide candidate sequences for hormone receptors, and a 2-base sliding window algorithm was applied to the extracted isoform consensus regions, thereby selecting 3,956 candidate sequences consisting of 19 bases.

[0136] In the list of selecte...

Embodiment 2

[0162] Example 2. Synthesis of double-stranded oligonucleotide constructs

[0163] The double-stranded oligonucleotide construct (SAMiRNA) produced in the present invention has a structure represented by the following structural formula.

[0164]

[0165] The synthesis process involves repeating cycles including deblocking, coupling, capping, and oxidation on a solid support (CPG) to which nucleosides are attached, thereby obtaining a single-stranded RNA with the desired sequence. An RNA synthesizer (384 synthesizer, BIONEER, Korea) was used for a series of synthesis processes of double-stranded oligo RNA.

[0166] The sense strand of the double-stranded oligonucleotide construct is produced by linking the phosphates that make up the DNA backbone using β-cyanoethyl phosphoramidites on polyethylene glycol (PEG)-CPG as a support. A diester bond to synthesize a double-stranded oligonucleotide construct with a sense strand containing polyethylene glycol bound to the 3' end and...

Embodiment 3

[0168] Example 3. Screening of SAMiRNA nanoparticles that induce RNAi by targeting the androgen receptor

[0169] 3.1 Fabrication of SAMiRNA nanoparticles and particle size analysis

[0170] Based on measurements of the size and polydispersity index of the SAMiRNAs obtained by particle size analysis using a Zetasizer Nano ZS (Malvern, UK) for 544 types of SAMiRNAs targeting the androgen receptor sequence synthesized in Example 2, random The sizes and polydispersity indices of selected SAMiRNA nanoparticles are shown in Table 4 below, and a representative graph thereof is shown in image 3 middle.

[0171] [Table 4]

[0172] Nanoparticle size and polydispersity index of androgen receptor-specific SAMiRNA

[0173] SEQ ID NO: code name size PDI 545 SAMi-Control 28±1.0 0.28±0.04 10 SAMi-AR#10 27.8±0.7 0.18±0.07

[0174] 3.2 Intracellular treatment of SAMiRNA nanoparticles

[0175] The human-derived prostate cancer cell line LNCaP was used...

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Abstract

The present invention relates to: a double stranded oligonucleotide construct having a structure of the form in which a hydrophilic material and a hydrophobic material are conjugated by a simple covalent bond or a linker-mediated covalent bond at both ends of a double stranded oligonucleotide in order to efficiently deliver an androgen receptor specific oligonucleotide into a cell; a nanoparticle which can be produced by self-assembling the double stranded oligonucleotide constructs in an aqueous solution by hydrophobic interaction; and a composition for preventing hair loss or for promoting hair growth comprising the double stranded oligonucleotide construct. The double stranded oligonucleotide construct comprising an androgen receptor specific oligonucleotide, and the composition for preventing hair loss or for promoting hair growth comprising the same as an active ingredient, according to the present invention, can inhibit the expression of an androgen receptor with high efficiency without side effects, and thus can have an excellent effect on the prevention of hair loss, especially androgenic hair loss, alopecia areata, and telogen alopecia and the promotion of hair growth.

Description

technical field [0001] The present invention relates to a double-stranded oligonucleotide construct comprising an androgen receptor specific sequence and a composition comprising the same for preventing hair loss and promoting hair growth, and more particularly to: a double-stranded An oligonucleotide construct configured such that a hydrophilic substance and a hydrophobic substance are conjugated to both ends of a double-stranded oligonucleotide via a simple covalent bond or a linker-mediated covalent bond to effectively to efficiently deliver nucleotides of an androgen receptor-specific sequence into cells; a nanoparticle capable of being produced by self-assembling a double-stranded oligonucleotide construct in aqueous solution via hydrophobic interactions; and a A composition for preventing hair loss and promoting hair growth, comprising the double-stranded oligonucleotide construct. Background technique [0002] Hair plays an important role in body protection and exter...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/60A61K47/58A61K47/54A61K47/69A61K31/713A61P17/14A61K8/60A61K8/86A61K8/81
CPCA61Q7/00A61K8/86A61K47/58A61P17/14A61K47/60A61K47/6933A61K47/6935A61K31/713A61K8/606A61K8/8176A61K2800/57A61K8/817A61K47/545A61K2800/413A61K47/59A61K47/595A61K8/84A61K8/88A61K47/26
Inventor 朴翰浯尹成一卞相轸李明美梁承惹
Owner BIONEER
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