title: Synthetically Modified Viral Capsids as Versatile Carriers for Use in Antibody-Based Cell Targeting.
abstract: The present study describes an efficient and reliable method for the preparation of MS2 viral capsids that are synthetically modified with antibodies using a rapid oxidative coupling strategy. The overall protocol delivers conjugates in high yields and recoveries, requires a minimal excess of antibody to achieve modification of more than 95% of capsids, and can be completed in a short period of time. Antibody-capsid conjugates targeting extracellular receptors on human breast cancer cell lines were prepared and characterized. Notably, conjugation to the capsid did not significantly perturb the binding of the antibodies, as indicated by binding affinities similar to those obtained for the parent antibodies. An array of conjugates was synthesized with various reporters on the interior surface of the capsids to be used in cell studies, including fluorescence-based flow cytometry, confocal microscopy, and mass cytometry. The results of these studies lay the foundation for further exploration of these constructs in the context of clinically relevant applications, including drug delivery and in vivo diagnostics.
authors.affiliation: †Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.
authors.forename: Adel M
authors.initials: AM
authors.lastname: ElSohly
authors.affiliation: †Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.
authors.forename: Chawita
authors.initials: C
authors.lastname: Netirojjanakul
authors.affiliation: †Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.|‡Materials Sciences Division, Lawrence Berkeley National Laboratories, Berkeley, California 94720-1460, United States.
authors.forename: Ioana L
authors.initials: IL
authors.lastname: Aanei
authors.affiliation: §Baxter Laboratory and Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, United States.
authors.forename: Astraea
authors.initials: A
authors.lastname: Jager
authors.affiliation: ∥Stanford Blood Center, Stanford School of Medicine, Palo Alto, California 94304, United States.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Bendall
authors.affiliation: †Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Farkas
authors.affiliation: §Baxter Laboratory and Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, United States.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Nolan
authors.affiliation: †Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.|‡Materials Sciences Division, Lawrence Berkeley National Laboratories, Berkeley, California 94720-1460, United States.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Francis
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002213:Capsid / Q000737:chemistry* / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D018796:Immunoconjugates / Q000378:metabolism; D018613:Microscopy, Confocal; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D014771:Virion / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D036022:Capsid Proteins; D018796:Immunoconjugates; D011956:Receptors, Cell Surface