Random Amphiphilic Polyaspartamide Derivatives for in vivo Administration of mRNA
발표자
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초록
내용
Transient and high therapeutic protein expression from messenger RNA (mRNA) is essential for achieving genome engineering, protein replacement therapy, and mRNA vaccines. We have developed an amphiphilic polyaspartamide randomly modified with diethylenetriamine (DET) and 2-cyclohexylethyl (CHE) moieties (PAsp(DET/CHE)). DET moiety provides high endosomal escape ability and CHE moiety optimizes polymer hydrophobicity between mRNA nanoparticle stability in the extracellular condition and mRNA release in the cytoplasm. Moreover, PAsp(DET/CHE) has relatively short degree of polymerization (DP) = 21 to reduce cytotoxicity. The PAsp(DET/CHE) polyplex with a hydrodynamic diameter of ~150 nm efficiently delivered luciferase mRNA mainly in the lung after intravenous administration, which induced more than 10-fold increase in mRNA transfection efficiency compared to commercially available Lipofectamine nanoparticles. This indicated that precise control of polymer hydrophobicity significantly improved particle stability in vivo and enhanced mRNA expression in target organ.