Chemically Modified RNA for Diabetic Wound Healing
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Solution Overview
Problem
Impaired wound healing in diabetes, particularly in diabetic foot ulcers, is a significant clinical challenge due to chronic inflammation and unsatisfactory efficacy of current therapeutic approaches, necessitating the development of more effective treatments.
Innovation Solution
A recombinant RNA molecule encoding polypeptides such as chitinase-3-like protein 1 (CHI3L1), fibroblast growth factor 2 (FGF-2), interleukin-2 ORF7, interleukin-2, and interleukin-17A, with chemical modifications like pseudouridine, is delivered via lipid nanoparticles (LNPs) to promote wound healing by enhancing expression of these proteins in wounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic approaches are used for diabetic foot ulcers, then treatment is provided, but efficacy is unsatisfactory
Solution Approach 1:
The patent applies parameter changes by chemically modifying the RNA molecules (e.g., pseudouridine substitution) to enhance their stability, reduce immunogenicity, and improve translation efficiency. These chemical parameter modifications enable the therapeutic RNA to maintain functionality longer and elicit stronger protein expression, directly addressing the unsatisfactory efficacy and slow healing rates of current treatments
2Quantity of substance
If RNA molecules are delivered to wounds, then protein expression is enhanced, but delivery efficiency is limited
Solution Approach 1:
The patent uses lipid nanoparticles as intermediary carriers to deliver the chemically modified RNA molecules to the wound site. These LNPs protect the RNA from degradation, facilitate cellular uptake, and enable efficient delivery of the therapeutic payload, thereby overcoming the limited delivery efficiency while achieving enhanced protein expression
3Reliability
If multiple polypeptides are encoded in recombinant RNA, then therapeutic effect is enhanced, but molecule complexity increases
Solution Approach 1:
The patent merges multiple therapeutic polypeptide coding sequences into single recombinant RNA molecules, allowing co-delivery and coordinated expression of multiple therapeutic agents (e.g., CHI3L1, FGF-2, IL-17A) from unified constructs. This merging approach enhances overall therapeutic effect while the chemical modifications simplify the molecules' interaction with cellular machinery
Data Source
AI summary
In certain aspects, the disclosure relates to a recombinant nucleic acid molecule (e.g. RNA molecule) encoding one or more polypeptides selected from the group consisting of chitinase-3-like protein 1 (CHI3L1), a fibroblast growth factor (FGF), interleukin-2 ORF7 (IL-2 ORF7), interleukin-2 (IL-2), an interleukin-17 (IL-17) protein, and an IL-17 receptor, wherein the recombinant RNA molecule comprises at least one chemical modification. Cells, pharmaceutical compositions and wound dressings comprising one or more of the recombinant nucleic acid molecules are also disclosed. Methods of promoting wound healing in a subject are further disclosed.