title: PEGylated cationic polylactides for hybrid biosynthetic gene delivery.
abstract: Genetic vaccination is predicated on the underlying principle that diseases can be prevented by the controlled introduction of genetic material encoding antigenic proteins from pathogenic organisms to elicit the formation of protective immune responses. Driving this process is the choice of carrier that is responsible for navigating the obstacles associated with gene delivery. In this work, we expand upon a novel class of hybrid biosynthetic gene delivery vectors that are composed of a biomaterial outer coating and a bacterial (Escherichia coli) inner core. Specifically, a series of newly developed biodegradable cationic polylactides (CPLAs) and their PEGylated variants were selected to investigate the role of low polydispersity index (PDI), charge density, and PEGylation upon hybrid vector assembly and gene delivery efficacy. Upon assembly, hybrid vectors mediated increased gene delivery beyond that of the individual bacterial vector in isolation, including assays with increasing medium protein content to highlight shielding properties afforded by the PEG-functionalized CPLA component. Furthermore, after extensive characterization of surface deposition of the polymer, results prompted a new model for describing hybrid vector assembly that includes cellular coating and penetration of the CPLA component. In summary, these results provide new options and insight toward the assembly and application of next-generation hybrid biosynthetic gene delivery vectors.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York , Buffalo, New York 14260-4200, United States.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Jones
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chen
authors.forename: Mingfu
authors.initials: M
authors.lastname: Chen
authors.forename: Anitha
authors.initials: A
authors.lastname: Ravikrishnan
authors.forename: Hanguang
authors.initials: H
authors.lastname: Zhang
authors.forename: Akhila
authors.initials: A
authors.lastname: Gollakota
authors.forename: Taichun
authors.initials: T
authors.lastname: Chung
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D002460:Cell Line; D018014:Gene Transfer Techniques / Q000009:adverse effects; D005818:Genetic Engineering; D005822:Genetic Vectors; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D051379:Mice; D008956:Models, Chemical; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D014162:Transfection; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D011091:Polyesters; D014614:Vaccines, Synthetic; D011092:Polyethylene Glycols; C033616:poly(lactide)
keywords: biosynthetic hybrid; cationic polymer; gene delivery; gene therapy; polylactide