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
