Many icosahedral and helical plant viruses produce at high levels in susceptible hosts, with yields in excess of 1 gram/Kg of leaves being common. They have been the subject of assembly studies for decades and have more recently been manipulated genetically through the use of infectious clones. High levels of heterologus expression in E. coli and yeast have also been achieved. Many are well characterized structurally with atomic coordinates available for the capsid protein subunits. These developments for cowpea mosaic virus made it a therapeutic agent for the development of inexpensive vaccines. Likewise, cowpea chlorotic mottle virus has been exploited as a molecular container with the internal properties modified by genetic alteration of the capsid protein. These qualities suggest that plant viruses can serve as a novel biomaterial. The goal of the proposed work is to now use these attributes of plant viruses and to exploit the particles as nanoblocks"""""""" and nano containers and to understand the principles of these alterations on their function. We will use plant virus particles as """"""""symmetric dendrimers? that can be chemically modified for developing a variety of targeted bio sensors, centers of catalysis, delivery systems, and imaging agents. We will generate tailored 2 and 3 dimensional arrays of these particles and these will serve as templates for a variety of nano materials. All of the basic technology of virus genetic modification is fully developed for the systems employed, as is the linkage chemistry for generating specific constellations of covalently attached functional groups. Six research groups will collaborate to create a wide range of modified plant virus particles and to explore their properties in vitro and in vivo. The expertise of these groups include synthetic and catalytic chemistry, materials science, the biochemistry and biophysics of nucleoprotein assembly, molecular virology, crystallography, electron cryo microscopy, image reconstruction and solution scattering methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB000432-01
Application #
6424655
Study Section
Special Emphasis Panel (ZRG1-BECM (01))
Program Officer
Kelley, Christine A
Project Start
2002-08-01
Project End
2007-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$1,089,392
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Prust, Cory J; Doerschuk, Peter C; Lander, Gabriel C et al. (2009) Ab initio maximum likelihood reconstruction from cryo electron microscopy images of an infectious virion of the tailed bacteriophage P22 and maximum likelihood versions of Fourier Shell Correlation appropriate for measuring resolution of spherical or cyli J Struct Biol 167:185-99
Steinmetz, N F; Lin, T; Lomonossoff, G P et al. (2009) Structure-based engineering of an icosahedral virus for nanomedicine and nanotechnology. Curr Top Microbiol Immunol 327:23-58
Prasuhn Jr, Duane E; Kuzelka, Jane; Strable, Erica et al. (2008) Polyvalent display of heme on hepatitis B virus capsid protein through coordination to hexahistidine tags. Chem Biol 15:513-9
Prasuhn Jr, Duane E; Singh, Pratik; Strable, Erica et al. (2008) Plasma clearance of bacteriophage Qbeta particles as a function of surface charge. J Am Chem Soc 130:1328-34
Miermont, Adeline; Barnhill, Hannah; Strable, Erica et al. (2008) Cowpea mosaic virus capsid: a promising carrier for the development of carbohydrate based antitumor vaccines. Chemistry 14:4939-47
Suci, Peter A; Varpness, Zachary; Gillitzer, Eric et al. (2007) Targeting and photodynamic killing of a microbial pathogen using protein cage architectures functionalized with a photosensitizer. Langmuir 23:12280-6
Lee, Junghoon; Doerschuk, Peter C; Johnson, John E (2007) Exact reduced-complexity maximum likelihood reconstruction of multiple 3-D objects from unlabeled unoriented 2-D projections and electron microscopy of viruses. IEEE Trans Image Process 16:2865-78
Liepold, Lars; Anderson, Stasia; Willits, Deborah et al. (2007) Viral capsids as MRI contrast agents. Magn Reson Med 58:871-9
Suci, Peter A; Berglund, Deborah L; Liepold, Lars et al. (2007) High-density targeting of a viral multifunctional nanoplatform to a pathogenic, biofilm-forming bacterium. Chem Biol 14:387-98
Douglas, Trevor; Young, Mark (2006) Viruses: making friends with old foes. Science 312:873-5

Showing the most recent 10 out of 34 publications