Method of preventing rheumatoid arthritis comprising administering polynucleotide encoding SSU72

Inventors

Cho, Mi-LaPark, Sung-HwanKWOK, Seung-KiCHOI, Jong-YoungLee, Seung-HunSEO, Hyeon-BeomMoon, Young-MeePark, Jin-SilPARK, Min-jungLee, Jin-kwanLee, Chang Woo

Assignees

Curogen Technology Co Ltd

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Publication Number

US-10925933-B2

Patent

Publication Date

2021-02-23

Expiration Date


Abstract

The present disclosure relates to a method of preventing rheumatoid arthritis comprising administering a polynucleotide encoding Ssu72.

Core Innovation

The invention relates to pharmaceutical and therapeutic use of Ssu72 as a gene therapy approach. It uses an expression vector comprising a polynucleotide encoding the Ssu72 protein for modulating immune responses, and the described therapeutic activity is linked to inhibition of STAT3 activity, including suppression of STAT3 phosphorylation.

The approach suppresses inflammatory cytokines and related factors associated with rheumatoid arthritis and Th17-related responses. It also promotes immunoregulatory responses by increasing IL-4 and IL-10 and by inducing Treg responses, including Foxp3.

The content further describes a screening and evaluation concept in which STAT3-activation is linked to Ssu72 gene/protein measurement. Supporting application results are reported in collagen-induced rheumatoid arthritis mouse models, including reduced arthritis indices and reduced cytokine expression in joints and lymphoid tissues.

Claims Coverage

The claim coverage includes one independent claim and one dependent refinement. The inventive concept centers on preventing rheumatoid arthritis by administering an expression vector encoding Ssu72, with the encoding polynucleotide specified as SEQ ID NO:2.

Preventing rheumatoid arthritis by administering an expression vector encoding Ssu72

A method for preventing an immune disease of rheumatoid arthritis comprising administering to a subject in need thereof an expression vector comprising a polynucleotide encoding the Ssu72 protein.

Encoding polynucleotide defined as SEQ ID NO:2

The method includes using a polynucleotide encoding the Ssu72 protein with a base sequence defined as SEQ ID NO:2.

Overall, the claims are directed to preventing rheumatoid arthritis by administering an expression vector that encodes the Ssu72 protein, with a dependent refinement specifying the encoding polynucleotide base sequence as SEQ ID NO:2.

Stated Advantages

Inhibits STAT3 activity, including suppression of STAT3 phosphorylation.

Suppresses inflammatory cytokines and related factors, including IL-17/IL-21, IL-1β/IL-6/IL-6R, TNF-α, and RANKL.

Promotes immunoregulatory responses by increasing IL-4 and IL-10 and inducing Treg, including Foxp3.

Reduces arthritis indices in collagen-induced rheumatoid arthritis mouse models.

Reduces cytokine expression in joints and lymphoid tissues.

Reduces osteoclast differentiation marker expression.

Alters immune cell populations, including increased Treg, decreased Th17, inhibition of Th1, and increased IL-10+ B cells.

Documented Applications

Preventing immune disease of rheumatoid arthritis in a subject in need thereof using an expression vector comprising a polynucleotide encoding Ssu72.

Use in collagen-induced rheumatoid arthritis mouse models showing reduced arthritis indices, reduced cytokine expression in joints and lymphoid tissues, reduced osteoclast differentiation marker expression, and altered immune cell populations.

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