PEGylated Cationic Polylactides for Hybrid Biosynthetic Gene Delivery
Autor: | Mingfu Chen, Charles H. Jones, Chih-Kuang Chen, Hanguang Zhang, Chong Cheng, Tai-Chun Chung, Anitha Ravikrishnan, Blaine A. Pfeifer, Akhila Gollakota |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Magnetic Resonance Spectroscopy
Genetic enhancement Polyesters Genetic Vectors Pharmaceutical Science Biocompatible Materials Gene delivery medicine.disease_cause Transfection Article Cell Line Polyethylene Glycols Mice Immune system Antigen Cations Drug Discovery Materials Testing medicine Animals Vector (molecular biology) Escherichia coli Genetics Vaccines Synthetic Chemistry Hybrid vector Gene Transfer Techniques Cell biology Models Chemical PEGylation Molecular Medicine Genetic Engineering |
Zdroj: | Mol Pharm |
Popis: | 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. |
Databáze: | OpenAIRE |
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