IRF5 Nuclear Localization Inhibition via Cell-Penetrating Peptide

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Solution Overview

Problem

Current treatments for systemic lupus erythematosus (SLE) are limited by the lack of a cure and the severe side effects associated with existing therapies, highlighting the need for new tools to investigate and treat SLE.

Innovation Solution

A polypeptide comprising a cell penetrating peptide sequence and an interferon regulatory factor 5 (IRF5) nuclear localization signal (NLS) sequence is developed, which inhibits IRF5 nuclear localization and subsequent pro-inflammatory cytokine expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments are used for SLE, then symptom control is achieved, but severe side effects occur

Engineering Contradiction:

Improvesymptom controlVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and targets the specific pathological mechanism of IRF5 nuclear translocation that drives SLE pathology, rather than using broad-spectrum immunosuppressants. By designing a peptide inhibitor that specifically blocks IRF5 nuclear localization signal (NLS), the treatment achieves disease control while avoiding the severe side effects associated with conventional therapies.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention applies local quality by creating a highly specific inhibitor that targets only the nuclear translocation step of IRF5, not the entire immune system. The cell-penetrating peptide conjugate with IRF5 NLS sequence selectively interferes with the specific pathological pathway while leaving other physiological functions intact, thereby reducing harmful side effects.

Inventive Principle:

Principle #3Local quality

2Reliability

If a polypeptide with cell penetrating peptide sequence and IRF5 NLS sequence is used, then IRF5 nuclear localization is inhibited, but the complexity of the molecule increases

Engineering Contradiction:

ImproveIRF5 nuclear localization inhibitionVSAvoidpolypeptide structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges two functional components into a single polypeptide molecule: a cell-penetrating peptide sequence (for cellular uptake) and an IRF5 nuclear localization signal sequence (for specific binding and inhibition). This combination allows the molecule to first enter cells and then specifically block IRF5 nuclear translocation, achieving the therapeutic effect while maintaining a relatively simple peptide structure.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The cell-penetrating peptide acts as an intermediary that facilitates the delivery of the IRF5 NLS sequence into the cell. This mediator approach allows the therapeutic agent to cross the cell membrane barrier and reach its intracellular target, solving the delivery problem without requiring complex delivery systems.

Inventive Principle:

Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The polypeptide effectively reduces IRF5 nuclear translocation and inflammatory cytokine production in both SLE patient-derived cells and animal models, offering a potential therapeutic approach for SLE.

Implementation Method 1

X is a cell penetrating peptide sequence... any amino acid sequence that facilitates cellular intake/uptake of the polypeptide

Methodology Applied

Scientific EffectCell penetrating peptide-mediated translocation:

Implementation Method 2

Z an IRF5 NLS sequence... any sequence that can mimic IRF5 nuclear translocation signals

Methodology Applied

Scientific EffectNuclear localization signal-mediated nuclear translocation:

Data Source

PatentUS20250188138A1Cell penetrating peptides that inhibit IRF5 nuclear localization

Publication Date: 2025.06.12 RUTGERS THE STATE UNIV

AI summary

The invention provides inhibitors of interferon regulatory factor 5 (IRF5) nuclear localization and methods of using the inhibitors to treat autoimmune diseases such as systemic lupus erythematosus (SLE).