Synthetically Modified Viral Capsids as Versatile Carriers for Use in Antibody-Based Cell Targeting
Autor: | Michelle E. Farkas, Adel M. ElSohly, Astraea Jager, Ioana L. Aanei, Garry P. Nolan, Sean C. Bendall, Matthew B. Francis, Chawita Netirojjanakul |
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Rok vydání: | 2015 |
Předmět: |
Immunoconjugates
viruses Pharmaceutical Science law.invention Drug Delivery Systems law Receptors Monoclonal Receptor Cancer Microscopy Microscopy Confocal biology medicine.diagnostic_test Chemistry Antibodies Monoclonal Flow Cytometry Capsid 5.1 Pharmaceuticals Confocal Cell Surface Female Development of treatments and therapeutic interventions Antibody Biotechnology Biomedical Engineering Breast Neoplasms Receptors Cell Surface Bioengineering Antibodies Article Fluorescence Flow cytometry Medicinal and Biomolecular Chemistry Confocal microscopy Breast Cancer Extracellular medicine Humans Mass cytometry Pharmacology Organic Chemistry Virion Molecular biology biology.protein Biophysics Capsid Proteins Biochemistry and Cell Biology Conjugate |
Zdroj: | Bioconjugate chemistry, vol 26, iss 8 |
ISSN: | 1520-4812 1043-1802 |
DOI: | 10.1021/acs.bioconjchem.5b00226 |
Popis: | 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. |
Databáze: | OpenAIRE |
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