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Short interfering ribonucleic acid (siRNA) for promoting scarless healing of skin wounds and application thereof

A technology of skin and composition, applied in the field of siRNA and its application to promote the healing of skin wounds without scars, which can solve the problems of impossible guarantee

Inactive Publication Date: 2011-04-27
SUZHOU SIRNAOMICS BIOPHARMACEUTICALS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0024] Importantly, it is not currently possible for researchers to ensure that candidate siRNAs that potentially target the mRNA sequence of a disease gene will show potent RNAi activity

Method used

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  • Short interfering ribonucleic acid (siRNA) for promoting scarless healing of skin wounds and application thereof
  • Short interfering ribonucleic acid (siRNA) for promoting scarless healing of skin wounds and application thereof
  • Short interfering ribonucleic acid (siRNA) for promoting scarless healing of skin wounds and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0077] Example 1. Taking the mouse eyeball neovascularization model research process as an example, it shows how to screen for inhibitory Active siRNA to form a multi-target siRNA cocktail process

[0078] Neovascularization in tissues is involved in many pathological processes, such as tumor expansion, rheumatoid arthritis, fundus macular degeneration, and granuloma and scar formation in skin trauma, etc. Therefore, we used siRNA drugs to inhibit neovascularization as a model system for siRNA therapy. The specific process is shown in this example: 1. Target gene selection, 2. siRNA design in computer, 3. In vivo and in vitro tests.

[0079] 1. Target gene selection.

[0080] Many genes are involved in the regulation of neovascularization, such as vascular endothelial growth factor (VEGF) and its receptor (VEGFR). According to the literature tracking and the survey of the same class of drugs in the current market, the target genes we selected include: mVEGF-A (XM_192823)...

Embodiment 2

[0113] Example 2.HKP polymer can enhance the local introduction of siRNA

[0114] Chemically synthesized histidine-lysine polymer (HKP) has been used for siRNA delivery in vitro and in vivo. Figure 3a The figure on the right shows the structural sequence of HKP: four polyamino acid branch chains are attached to the trimeric lysine backbone. Polyamino acid branches are repeated in fixed arrangement and length by histidine, lysine or asparagine. The two types of HKPs used in the study are H3K4b and PT73 with the structure (R)K(R)-K(R)-(R)K(X), where R=KHHHKHHHKHHHKHHHK in H3K4b and R=KHHHKHHHNHHHNHHHN in PT73, X=C(O)NH2, K=lysine, H=histidine, N=asparagine. Figure 3a The image on the left is a scanning electron microscope image. When the HKP aqueous solution and siRNA are mixed at a mass ratio of 4:1, nanoparticles with an average diameter of 100-200 nm are automatically formed. The HKP-siRNA aqueous solution is translucent, without obvious precipitation and aggregation,...

Embodiment 3

[0118] Example 3. HoxB13 KO mice show rapid wound healing and less scarring

[0119] HoxB13 KO mice (gifted by Dr.Mario R.Capecchi) are an effective platform to verify the function of HoxB13 gene. In order to track the dynamic changes of tissue structure in the repair process of skin tissue after injury, we established a lip surgical split model in HoxB13 KO mice to simulate cleft palate of rabbit lip. Normal lip skin was stained by hematoxylin-eosin (HE) as Figure 4 shown. Under general anesthesia and aseptic conditions, a single 0.5 cm full-thickness skin incision wound was made on the skin and front teeth of HoxB13KO and wild-type mice (8-16 weeks old), and then the wound was sutured with 6.0 nylon, This simulates a cleft palate of a rabbit lip. Skin wound biopsies were taken at 20, 30, and 60 days after injury, and the collagen structure was analyzed by Masson Trichrome staining, as Figure 5 . On the 20th day (B-Day20) and the 30th day (B-Day30), WT mice had dense...

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Abstract

The invention discloses a short interfering ribonucleic acid (siRNA) molecule for promoting scarless healing of skin wounds, a cocktail combination of a plurality of siRNA molecules targeting a plurality of related genes of scarless healing of wounds, and a pharmaceutical composition taking the siRNA molecule or the cocktail combination thereof as an active ingredient. Proven by cell experiments and mouse and pig skin wound models, the pharmaceutical composition can promote scarless healing of skin wounds resulted from traumata, surgical operation, or diabetes skin ulcer and the like, wherein the siRNA molecule can target genes causing pathological repair of wounds or adverse reactions; the siRNA double chains have different lengths and different tail ends and can target a homologous sequence of the same gene of cells of human, mouse and pig; the plurality of siRNAs in the cocktail combination can simultaneously inhibit various related genes of wound inflammation and revascularization, and has more obvious drug effects; and pharmaceutical carriers such as histidine-lysine polymer, dendritic polymer or liposome and the like in the pharmaceutical composition in a nanoparticle form can enhance the siRNA to be introduced into the skin tissue.

Description

technical field [0001] The invention relates to an siRNA molecule for promoting skin wound healing without scarring, a cocktail combination of multiple siRNA molecules targeting multiple genes related to wound healing without scarring, and a pharmaceutical composition using the siRNA molecule or the cocktail combination thereof as an active ingredient. Background technique [0002] The skin is the largest organ of the body, consisting of the lower inner layer (dermis) and the outer epidermis (epidermis). The basic function of the skin is to protect the body from the external environment. When the integrity of the body's skin is damaged in a large area due to injury or disease, the loss of the main barrier function can lead to the death of the body. In the United States, more than 1.25 million burn patients and 6.5 million suffer from chronic skin ulcers due to compression, venous stasis, or diabetes each year. The primary goal of wound treatment is rapid healing and restora...

Claims

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Application Information

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IPC IPC(8): C12N15/113A61K48/00A61P17/02
Inventor 徐军沈艳华唐盛高陆阳
Owner SUZHOU SIRNAOMICS BIOPHARMACEUTICALS CO LTD
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