In this publication, Ben Swanson reports a novel library of pH-sensitive derivatives of Rhodamine-6G. These probes are versatile in terms of both range of pH-sensitivity (i.e., pKa) and chemical functionality, allowing conjugation to small molecules, proteins, nanoparticles, and scaffolds. One potential application is visualization of endocytosis and endosomal escape of NPs (bottom image).
In this publication, Jacob Myerson demonstrates accumulation of nanoparticles with agglutinated protein (NAPs) in neutrophils in the inflamed lungs. This includes azide liposomes conjugated to surface antibody heavily modified with the hydrophobic cyclooctyne, DBCO (top image). The enhanced uptake of NAPs is applied to create a molecular imaging strategy for inflamed lungs (bottom image) and for therapeutic delivery.
Our first article in the New England Journal of Medicine! This publication reports the results of C3PO, the SIREN-sponsored multi-center, RCT of convalescent plasma in COVID-19 patients who presented to the ED and were stable enough for outpatient management, but at high-risk for subsequent complications.
In this publication, Meu Pornnoppadol reports a potential pitfall in variable domain sequencing of a hybridoma derived monoclonal antibody. The antigen specific variable light chain is found to have ~95% sequence identity to the aberrant kappa chain of the Sp2/0 myeloma.
In this publication, Boya Zhang describes a key technology for our laboratory, the site specific and monomolecular modification of recombinant proteins. This technique allows fluorescence and radiolabel modification without affecting protein function (e.g., binding affinity) and conjugation of proteins with defined orientation and stoichiometry.
In this manuscript, Raisa Kiseleva describes optimization of endothelial surface delivery of biotherapeutic cargo. Using thrombomodulin as a model therapeutic, she demonstrates that bivalent engagement of the cell adhesion molecules PECAM-1 and ICAM-1 -- ideally with oriented, site-specific conjugation -- results in prolonged anchoring of cargo to the luminal surface membrane.
In this publication, Patrick Glassman engineers nanobody (VHH) affinity ligands to investigate the the impact of key affinity ligand characteristics (affinity, valence, circulation time) on biodistribution, pharmacokinetics, and cargo delivery. While bivalent binding to the target molecule (VCAM-1) is shown to increase affinity and targeting to spleen and brain, prolongation of circulation time via introduction of an albumin-binding arm demonstrates the greatest increase in target organ uptake.