Non-viral gene therapy using RNA interference with PDGFR-α mediated epithelial-mesenchymal transformation for...

Area of Science:

• Ophthalmology
• Biotechnology
• Gene Therapy

Background:

• Fibrotic eye diseases, such as proliferative vitreoretinopathy (PVR), cause severe vision loss by damaging ocular structures.
• These conditions involve epithelial-mesenchymal transition (EMT), where epithelial cells transform into mesenchymal cells, leading to fibrosis.
• Current treatments are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate polyethylene glycol grafted branched Polyethyleneimine (PEI-g-PEG) as a non-viral gene vector for PVR therapy.
• To investigate the anti-fibroblastic effects of PEI-g-PEG/PDGFR-α shRNA in vitro and in vivo.
• To assess the potential of RNA interference (RNAi) targeting platelet-derived growth factor alpha receptor (PDGFR-α) in preventing EMT in retinal pigment epithelium (RPE) cells.

Main Methods:

• Preparation of PEI-g-PEG/PDGFR-α shRNA gene complexes via electrostatic conjugation.
• In vitro studies assessing biocompatibility, cellular uptake, gene expression, and EMT inhibition.
• In vivo animal models to evaluate the efficacy in inhibiting PVR fibroproliferative membranes.

Main Results:

• Successful preparation and characterization of gene complexes.
• PEI-g-PEG demonstrated excellent biocompatibility, efficient cellular uptake, and successful gene expression in vitro.
• PEI-g-PEG/PDGFR-α shRNA effectively inhibited EMT in vitro and suppressed fibroproliferative membrane progression in vivo.

Conclusions:

• PEI-g-PEG serves as a safe and effective non-viral gene vector for PVR treatment.
• RNAi targeting PDGFR-α with PEI-g-PEG/PDGFR-α shRNA offers a promising strategy to inhibit EMT and combat fibrotic eye diseases.
• This approach presents a feasible clinical strategy for developing novel treatments for vision-threatening fibrotic ocular conditions.