Novel Nanopolymer RNA Therapeutics Normalize Human Diabetic Corneal Wound Healing and Epithelial Stem Cells

Overview

Journal Nanomedicine

Publisher Elsevier

Specialties Biomedical Engineering
Biotechnology

Date 2020 Nov 12

PMID 33181273

Citations 12

Authors

Andrei A Kramerov

Ruchi Shah

Hui Ding

Eggehard Holler

Sue Turjman

Yaron S Rabinowitz

Sean Ghiam

Ezra Maguen

Clive N Svendsen

Mehrnoosh Saghizadeh

Julia Y Ljubimova

Alexander V Ljubimov

Affiliations

Soon will be listed here.

Abstract

Human diabetic corneas develop delayed wound healing, epithelial stem cell dysfunction, recurrent erosions, and keratitis. Adenoviral gene therapy modulating c-Met, cathepsin F and MMP-10 normalized wound healing and epithelial stem cells in organ-cultured diabetic corneas but showed toxicity in stem cell-enriched cultured limbal epithelial cells (LECs). For a safer treatment, we engineered a novel nanobiopolymer (NBC) that carried antisense oligonucleotide (AON) RNA therapeutics suppressing cathepsin F or MMP-10, and miR-409-3p that inhibits c-Met. NBC was internalized by LECs through transferrin receptor (TfR)-mediated endocytosis, inhibited cathepsin F or MMP-10 and upregulated c-Met. Non-toxic NBC modulating c-Met and cathepsin F accelerated wound healing in diabetic LECs and organ-cultured corneas vs. control NBC. NBC treatment normalized levels of stem cell markers (keratins 15 and 17, ABCG2, and ΔNp63), and signaling mediators (p-EGFR, p-Akt and p-p38). Non-toxic nano RNA therapeutics thus present a safe alternative to viral gene therapy for normalizing diabetic corneal cells.

Citing Articles

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