Systemic delivery of mRNA and DNA to the lung using polymer-lipid nanoparticles

Non-viral vectors offer the potential to deliver nucleic acids including mRNA and DNA into cells in vivo . However, designing materials that effectively target organs then desired compartments within cell remains a challenge. Here we develop polymeric can be optimized for either transcription nucleus or translation cytosol. We synthesized poly(beta amino ester) terpolymers (PBAEs) with modular changes monomer chemistry investigate influence on acid delivery. identified two PBAEs single change as being effective (D-90-C12-103) (DD-90-C12-103) delivery lung endothelium following intravenous injection mice. Physical properties such particle size charge did not account difference transfection efficacy. endosome co-localization studies revealed D-90-C12-103 nanoparticles resided late endosomes greater extent than DD-90-C12-103. compared luciferase expression observed that, even vectors, peak luminescence using was orders of magnitude pDNA lungs mice systemic This study indicates different require tailored further support intracellular materials.