Dual-Surface-Modified Bacteriophage MS2 as an Ideal Scaffold for a Viral Capsid-Based Drug Delivery System
- 30 June 2007
- journal article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 18 (4), 1140-1147
- https://doi.org/10.1021/bc070006e
Abstract
With the development of covalent modification strategies for viral capsids comes the ability to convert them into modular carrier systems for drug molecules and imaging agents. With this overall goal in mind, we have used two orthogonal modification strategies to decorate the exterior surface of genome-free MS2 capsids with PEG chains, while installing 50−70 copies of a fluorescent dye inside as a drug cargo mimic. Despite the very high levels of modification, the capsids remained in the assembled state, as determined by TEM, size-exclusion chromatography, and dynamic light scattering analysis. The ability of the polymer coating to block the access of polyclonal antibodies to the capsid surface was probed using a sandwich ELISA, which indicated a 90% reduction in binding. Further experiments indicated that biotin groups placed at the distal ends of the polymer chains were still capable of binding to streptavidin, despite their proximity to the PEG layer. Finally, a modular strategy was developed for the attachment of small-molecule targeting groups to the polymer chains through an efficient oxime formation reaction. As a result of these studies, a robust and versatile new platform has emerged for the potential delivery of therapeutic cargo.Keywords
This publication has 14 references indexed in Scilit:
- Dual-Surface Modification of the Tobacco Mosaic VirusJournal of the American Chemical Society, 2005
- Natural Nanochemical Building Blocks: Icosahedral Virus Particles Organized by Attached OligonucleotidesNano Letters, 2004
- Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted CytotoxinThe Journal of Organic Chemistry, 2004
- Interior Surface Modification of Bacteriophage MS2Journal of the American Chemical Society, 2004
- The dawning era of polymer therapeuticsNature Reviews Drug Discovery, 2003
- “Stealth” Adenoviruses Blunt Cell-Mediated and Humoral Immune Responses against the Virus and Allow for Significant Gene Expression upon Readministration in the LungJournal of Virology, 2001
- The Refined Structure of Bacteriophage MS2 at 2·8 Å ResolutionJournal of Molecular Biology, 1993
- Multiple presentation of foreign peptides on the surface of an RNA-free spherical bacteriophage capsidJournal of General Virology, 1993
- The three-dimensional structure of the bacterial virus MS2Nature, 1990
- Purification and properties of bacteriophage MS2 and of its ribonucleic acidJournal of Molecular Biology, 1963