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This study reports on the design and characterization of new ionizable amino\u2010polyesters (APEs), synthesized via ring opening polymerization (ROP) of lactones with tertiary amino\u2010alcohols that enable tissue and cell type selective delivery of mRNA. With a diverse library of APEs formulated into lipid nanoparticles (LNP), structure\u2010activity parameters crucial for efficient transfection are established and APE\u2010LNPs are identified that can preferentially home to and elicit effective mRNA expression with low in vivo toxicity in lung endothelium, liver hepatocytes, and splenic antigen presenting cells, including APE\u2010LNP demonstrating nearly tenfold more potent systemic mRNA delivery to the lungs than vivo\u2010jetPEI. Adopting tertiary amino\u2010alcohols to initiate ROP of lactones allows to control polymer molecular weight and obtain amino\u2010polyesters with narrow molecular weight distribution, exhibiting batch\u2010to\u2010batch consistency. All of which highlight the potential for clinical translation of APEs for systemic mRNA delivery and demonstrate the importance of employing controlled polymerization in the design of new polymeric nanomaterials to improve in vivo nucleic acid delivery.<\/jats:p>","DOI":"10.1002\/adma.201801151","type":"journal-article","created":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T12:53:05Z","timestamp":1530795185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Ionizable Amino\u2010Polyesters Synthesized via Ring Opening Polymerization of Tertiary Amino\u2010Alcohols for Tissue Selective mRNA Delivery"],"prefix":"10.1002","volume":"30","author":[{"given":"Piotr S.","family":"Kowalski","sequence":"first","affiliation":[{"name":"David H. 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