%ACapasso Palmiero, Umberto [David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA 02139 USA, Department of Chemistry Materials and Chemical Engineering Politecnico di Milano Via Mancinelli 7 20131 Milano Italy]%AKaczmarek, James [David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA 02139 USA, Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA]%AFenton, Owen [David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA 02139 USA, Department of Chemistry Massachusetts Institute of Technology Cambridge MA 02139 USA]%AAnderson, Daniel [David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA 02139 USA, Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA, Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge MA 02139 USA, Harvard and MIT Division of Health Science and Technology Massachusetts Institute of Technology Cambridge MA 02139 USA]%BJournal Name: Advanced Healthcare Materials; Journal Volume: 7; Journal Issue: 14; Related Information: CHORUS Timestamp: 2023-09-18 02:56:15 %D2018%IWiley Blackwell (John Wiley & Sons) %JJournal Name: Advanced Healthcare Materials; Journal Volume: 7; Journal Issue: 14; Related Information: CHORUS Timestamp: 2023-09-18 02:56:15 %K %MOSTI ID: 10061694 %PMedium: X %TPoly(β‐amino ester)‐ co ‐poly(caprolactone) Terpolymers as Nonviral Vectors for mRNA Delivery In Vitro and In Vivo %XAbstract

The production of new proteins with messenger RNA (mRNA) has gained a broad interest due to its potential for addressing a wide range of diseases. Here, the design and characterization of novel ionizable poly(β‐amino ester)‐co‐poly(caprolactone) terpolymers, synthesized via the combination of the ring opening polymerization and the Michael step‐growth polymerization, are reported. The versatility of this method is demonstrated by varying the number of caprolactone units attached to each poly(β‐amino ester) (PBAE) terpolymer. The ability of the novel poly‐caprolactone (PCL)‐based PBAE materials to deliver mRNA is shown to depend on the physiochemical characteristics of the material, such as lipophilicity, as well as the formulation method used to complex the polymer with the oligonucleotide. This latter variable represents a previously unstudied aspect of PBAE library screens that can play an important role in identifying true top candidates for nucleic acid delivery. The most stable terpolymer is injected intravenously (IV) in mice and shows a transfection efficacy several times higher than the polyethylenimine (PEI) which is focused in the spleen, opening the possibility to use these biodegradable carriers in the intravenous delivery of antigen‐encoding mRNA for cancer immunotherapy and vaccination.

%0Journal Article