C-Rel-specific siRNA and its use for preventing and treating autoimmune psoriasis

Patent metadata

Field	Value
Publication number	US-10081810-B2
Application number	US-201715680449-A
Country	US
Kind code	B2
Filing date	Aug 18, 2017
Priority date	Oct 16, 2015
Publication date	Sep 25, 2018
Grant date	Sep 25, 2018

Abstract

The present invention provides a c-Rel-specific siRNA and its use for preventing and treating autoimmune psoriasis. In particular, the c-Rel-specific siRNAs have sequences as shown in SEQ ID Nos. 1-2 or SEQ ID Nos. 3-4. In the present invention, small interfering RNA (siRel) specific to c-Rel are employed to inhibit c-Rel biosynthesis, and prevent and treat autoimmune psoriasis by inhibiting inflammatory factors relating to IL-23/IL-17A inflammatory axis.

First claim

The invention claimed is:

1. A method for preventing and/or treating autoimmune psoriasis of human, comprising a step of administrating to a subject in need thereof an effective amount of c-Rel-specific small interfering RNAs to inhibit c-Rel biosynthesis, so as to inhibit IL-23/IL-17A inflammatory axis in the subject with psoriasis
wherein a delivery method of the small interfering RNA is selected from a group consisting of intravenous administration, intradermal application within skin lesion areas, subcutaneous application within the skin lesion areas, and on-skin application within the skin lesion areas,
wherein a dosage of the c-Rel-specific small interfering RNAs administrated intravenously is 0.3 mg/kg, given at a frequency of once every three weeks;
a dosage of the c-Rel-specific small interfering RNAs administrated intradermally is 8 mg in a volume of 2 ml, given at a frequency of once every one week;
a dosage of the c-Rel-specific small interfering RNAs administrated subcutaneously is 16 mg in a volume of 4 ml, given at a frequency of once every one week; and
a concentration of the c-Rel-specific small interfering RNAs applied on the skin is 10 nM, given at a frequency of 1-3 times every one day.

2. The method according to claim 1 , wherein the c-Rel-specific small interfering RNAs have sequences as shown in SEQ ID Nos. 1-2 or SEQ ID Nos. 3-4.

3. The method according to claim 1 , wherein a nano-material is used to carry the c-Rel-specific small interfering RNAs and transport them to a cytoplasm.

4. The method according to claim 3 , wherein the nano-material is a PEG-PLL-PLLeu tri-block copolymer nano-micelle.

5. The method according to claim 4 , wherein the dosage of the c-Rel-specific small interfering RNAs administrated intravenously is 0.3 mg/kg, and a corresponding dosage of the nano-micelle is 4.5 mg/kg, given at a frequency of once every three weeks; the dosage of the c-Rel-specific small interfering RNAs administrated intradermally is 8 mg, and a corresponding dosage of the nano-micelle is 8 mg, given at a volume of 2 ml and a frequency of once every one week; the dosage of the c-Rel-specific small interfering RNAs administrated subcutaneously is 16 mg, and a corresponding dosage of the nano-micelle is 16 mg, given at a volume of 4 ml and a frequency of once every one week; and a concentration of the c-Rel-specific small interfering RNAs applied on the skin is 10 nM, and a corresponding dosage of the nano-micelle is 10 μg/ml, given at a frequency of 1-3 times every one day, wherein 0.5 ml of a c-Rel-specific small interfering RNAs-nano-micelle suspension is applied per 500 square centimeters for each application.

6. A method for preventing and/or treating autoimmune psoriasis, comprising a step of administrating to a subject in need thereof an effective amount of c-Rel-specific small interfering RNAs to inhibit c-Rel biosynthesis, so as to inhibit IL-23/IL-17A inflammatory axis in the subject,
wherein the subject is a mammal,
wherein for in vitro administration, the c-Rel-specific small interfering RNAs used at a concentration of 10-100 nM; for in vivo administration, for treatment of mild psoriasis, each mammal is administered intraperitoneally 500 pmol c-Rel-specific small interfering RNAs, given at a frequency of once every two days; for treatment of moderate psoriasis, each mammal is administered intraperitoneally 500 pmol c-Rel-specific small interfering RNAs, given at a frequency of once every one day.

7. The method according to claim 6 , wherein the c-Rel-specific small interfering RNAs have sequences as shown in SEQ ID Nos. 1-2 or SEQ ID Nos. 3-4.

8. The method according to claim 6 , wherein a nano-material is used to carry the c-Rel-specific small interfering RNAs and transport them to the cytoplasm.

9. The method according to claim 6 , wherein the nano-material is a PEG-PLL-PLLeu tri-block copolymer nano-micelle.

10. The method according to claim 9 , wherein the subject is a mouse.

11. The method according to claim 10 , wherein, for in vitro administration, the c-Rel-specific small interfering RNAs is used at a concentration of 10-100 nM, and the nano-micelle is used at a concentration of 10-20 μg/ml; for in vivo administration, for the treatment of mild psoriasis, each mouse is administered intraperitoneally 500 pmol of the c-Rel-specific small interfering RNAs, corresponding to 100 μg of nano-micelle, given at a frequency of once every two days; for the treatment of moderate psoriasis, each mouse is administered intraperitoneally 500 pmol of the c-Rel-specific small interfering RNAs, corresponding to 100 μg of nano-micelle, given at a frequency of once every one day.

Assignees

• Shenzhen Inst Adv Tech
• Univ Pennsylvania
• Shenzhen Inst Adv Tech

Inventors

• Ruan Qingguo
• Chen Youhai H
• Fan Tingting
• Ma Yifan
• Cai Lintao
• Wang Shaowen
• Wan Xiaochun

Classifications

• A61K47/18 Primary

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• A61K9/0014

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title