title: Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo.
abstract: Safe and effective delivery is required for siRNA and mRNA-based therapeutics to reach their potential. Here, we report on the development of poly(glycoamidoamine) brush nanoparticles as delivery vehicles for siRNA and mRNA. These polymers were capable of significant delivery of siRNA against FVII and mRNA-encoding erythropoietin (EPO) in mice. Importantly, these nanoparticles were well-tolerated at their effective dose based on analysis of tissue histology, systemic cytokine levels, and liver enzyme chemistry. The polymer brush nanoparticles reported here are promising for therapeutic applications.
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Dong
authors.forename: J Robert
authors.initials: JR
authors.lastname: Dorkin
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Wang
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Chang
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Tang
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Junghoon
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biotechnology and Food Engineering, Technion Institute of Technology and the Russell Berrie Nanotechnology Institute , Haifa 32000, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Abutbul-Ionita
authors.affiliation: Department of Biotechnology and Food Engineering, Technion Institute of Technology and the Russell Berrie Nanotechnology Institute , Haifa 32000, Israel.
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
authors.affiliation: Shire , 300 Shire Way, Lexington, Massachusetts 02421, United States.
authors.forename: Frank
authors.initials: F
authors.lastname: DeRosa
authors.affiliation: Shire , 300 Shire Way, Lexington, Massachusetts 02421, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Heartlein
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, §Department of Biology, and ∥Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000037:antagonists & inhibitors / Q000235:genetics; D005167:Factor VII / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D012333:RNA, Messenger / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004921:Erythropoietin; D005167:Factor VII
keywords: erythropoietin; mRNA; nanomaterial; polymer brush; siRNA