Abstract
Safe and efficient nucleic acid delivery to targeted cell populations remains a significant unmet need in the fields of cell and gene therapy. Towards this end, we pursued Adenoviral vectors genetically modified with the “DogTag” molecular glue peptide, which forms a spontaneous covalent bond with its partner protein, “DogCatcher”. Genetic fusion of DogCatcher to single-domain or single-chain antibodies allowed covalent tethering of the antibody at defined locales on the vector capsid. This modification allowed simple, effective and exclusive targeting of the vector to cells bound by the linked antibody. This dramatically enhanced gene transfer into primary B and T cells in vitro and in vivo in mice. These studies form the basis of a novel method for targeting Adenovirus that is functional in stringent in vivo contexts and can be combined with additional well characterized Adenovirus modifications towards applications in cell engineering, gene therapy, vaccines, oncolytics, and others.
Competing Interest Statement
Hongjie Guo is the founder and Chief Scientific Officer of Tiger Biologics, LLC, a protein production company. Paul J. Rice-Boucher. David T. Curiel, and Zhi Hong Lu are co-inventors on a patent application describing the use of the Ad-Ab system for B cell targeting and engineering.
Data availability statement
Plasmids used in this study are to be deposited in AddGene. Flow cytometry data is available upon reasonable request. All other data can be found in the main text or Supplemental.
