In vitro incorporation of a cell-binding protein to a lentiviral vector using an engineered split intein enables targeted delivery of genetic cargo. Academic Article uri icon

abstract

  • Gene therapy represents a promising therapeutic paradigm for addressing many disorders, but the absence of a vector that can be robustly and reproducibly functionalized with cell-homing functionality to mediate the delivery of genetic cargo specifically to target cells following systemic administration has stood as a major impediment. In this study, a high-affinity protein-protein pair comprising a splicing-deficient naturally split intein was used as molecular Velcro to append a HER2/neu-binding protein (DARPin) onto the surface of a binding-deficient, fusion-competent lentivirus. HER2/neu-specific lentiviruses created using this in vitro pseudotyping approach were able to deliver their genetic reporter cargo specifically to cells that express the target receptor at high levels in a co-culture. We envision that the described technology could provide a powerful, broadly applicable platform for the incorporation of cell-targeting functionality onto viral vectors.

published proceedings

  • Biotechnol Bioeng

altmetric score

  • 1

author list (cited authors)

  • Chamoun-Emanuelli, A. M., Wright, G., Roger, S., Mnch, R. C., Buchholz, C. J., & Chen, Z.

citation count

  • 2

complete list of authors

  • Chamoun-Emanuelli, Ana M||Wright, Gus||Roger, Smith||M√ľnch, Robert C||Buchholz, Christian J||Chen, Zhilei

publication date

  • December 2015

publisher