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Folic acid-mediated targeting of cowpea mosaic virus particles to tumor cells.

ABSTRACT: Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and redirect CPMV particles to cells of interest, we attached a folic acid-PEG conjugate by using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV-specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors.

SUBMITTER: Destito G

PROVIDER: S-EPMC2293326 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Folic acid-mediated targeting of cowpea mosaic virus particles to tumor cells.

Destito Giuseppe G Yeh Robert R Rae Chris S CS Finn M G MG Manchester Marianne M

Chemistry & biology 20071001 10

Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and redirect CPMV particles to cells of interest, we attached a folic acid-PEG conjugate by using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moi ...[more]

PMID: 17961827

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Cowpea Mosaic Virus

Project description:Cowpea mosaic virus (CPMV) is the type member of the genus Comovirus, which comprises one of three genera of the family Comoviridae. The genome of CPMV consists of two molecules of positive-strand RNA, which are separately encapsidated in isometric particles consisting of 60 copies each of two types of coat protein. Since its initial isolation, CPMV has been extensively studied from both a genetic and structural point of view and has become a paradigm for plant viruses that express their genome through the synthesis and processing of precursor polyproteins. In this regard, as well as in its particle structure, CPMV resembles other members of the family Picornaviridae. More recently, the virus has been used for a number of biotechnological applications.

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Crystal Structure and Proteomics Analysis of Empty Virus-like Particles of Cowpea Mosaic Virus.

Project description:Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C terminus of the small (S) subunit. The intact C terminus of the S subunit plays a critical role in enabling the efficient assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle formation. In addition, we report the results of mass spectrometry-based proteomics analysis of coat protein subunits from CPMV eVLPs and virions that identify the C termini of S subunits undergo proteolytic cleavages at multiple sites instead of a single cleavage site as previously observed.

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