Nonclinical pharmacokinetics and biodistribution of VSV-GP using methods to decouple input drug disposition and viral replication
Richard Dambra, Andrea Matter, Kaitlynn Graca, Saeed Salehin Akhand, Saurin Mehta, Ashlee Bell-Cohn, Joyce M. Swenson, Sadia Abid, Dongyue Xin, Cedric Lewis, Luke Coyle, Min Wang, Kathleen Bunosso, Michelle Maugiri, Richard Ruiz, Corey M. Cirillo, Birgit Fogal, Christine Grimaldi, Adam Vigil, Charles Wood, Joseph Ashour
Abstract
hybridization method using strand-specific probes and assessed their spatiotemporal distribution in tissues. This latter approach demonstrated that distribution, transcription, and replication localized to tissue-resident macrophages, indicating their role in PK and BD. Ultimately, our study results in a refined PK/BD profile for a replicating OV, new proposed PK parameters, and deeper understanding of OV PK/BD using unique approaches that could be applied to other replicating vectors.