Genetically Engineered Biomimetic Nanoparticles for Targeted Delivery of mRNA to Treat Rheumatoid Arthritis

Area of Science:

• Biomedical Engineering
• Molecular Therapy
• Immunology

Background:

• Rheumatoid arthritis (RA) involves persistent inflammation and joint damage.
• Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is a therapeutic target for RA.
• Current mRNA therapies for RA face challenges with stability and targeted delivery to synovial tissue.

Purpose of the Study:

• To develop a biomimetic carrier for effective delivery of mRNA-PTEN to RA joints.
• To create a therapeutic platform that inhibits pro-inflammatory cytokines and upregulates PTEN.
• To evaluate the efficacy of the MR@P-mPTEN construct in treating RA in vitro and in vivo.

Main Methods:

• Genetically engineered biomimetic membrane-coated mRNA carrier (MR@P-mPTEN) for mRNA-PTEN delivery.
• Overexpression of TNF-α receptors on macrophage biomimetic membranes for decoy purposes.
• In vitro and in vivo studies to assess stability, targeting, PTEN pathway activation, and inhibition of synovitis and joint damage.
• Clinical micro-computed tomography and histological analyses for treatment effect confirmation.

Main Results:

• MR@P-mPTEN demonstrated good stability and effective RA targeting in vivo.
• The construct competitively bound TNF-α and activated the PTEN pathway.
• MR@P-mPTEN successfully inhibited synovitis and joint damage, confirmed by imaging and histology.
• The platform inhibited pro-inflammatory cytokines and upregulated PTEN protein expression.

Conclusions:

• The MR@P-mPTEN platform offers a promising combination strategy for RA treatment.
• This biomimetic therapeutic approach effectively targets RA by modulating PTEN and inhibiting inflammation.
• The study presents a novel platform for enhancing mRNA delivery and efficacy in treating joint diseases like RA.