Novel nanopolymer RNA therapeutics normalize human diabetic corneal wound healing and epithelial stem cells'

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 (keratin 15 and 17, ABCG2, and Delta Np63), 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. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

Human diabetic corneas face delayed wound healing and stem cell dysfunction, but researchers have developed a novel nanobiopolymer that can safely accelerate healing and normalize cellular function. This non-toxic nano RNA therapeutics present a safe alternative to viral gene therapy for diabetic corneal cells.