Advanced genetic engineering to achieve in vivo targeting of adenovirus utilizing camelid single domain antibody

Myungeun Lee, Zhi Hong Lu, Charles B. Shoemaker, Jacqueline M. Tremblay, Bradley St. Croix, Steven Seaman, Rebeca Gonzalez-Pastor, Elena A. Kashentseva, Igor P. Dmitriev, David T. Curiel

Research output: Contribution to journalArticlepeer-review

Abstract

For the developing field of gene therapy the successful address of the basic requirement effective gene delivery has remained a critical barrier. In this regard, the “Holy Grail” vector envisioned by the field's pioneers embodied the ability to achieve efficient and specific in vivo gene delivery. Functional linkage of antibody selectivity with viral vector efficiency represented a logical strategy but has been elusive. Here we have addressed this key issue by developing the technical means to pair antibody-based targeting with adenoviral-mediated gene transfer. Our novel method allows efficient and specific gene delivery. Importantly, our studies validated the achievement of this key vectorology mandate in the context of in vivo gene delivery. Vectors capable of effective in vivo delivery embody the potential to dramatically expand the range of successful gene therapy cures.

Original languageEnglish
Pages (from-to)106-113
Number of pages8
JournalJournal of Controlled Release
Volume334
DOIs
StatePublished - Jun 10 2021

Keywords

  • Adenoviral vectors (Ad)
  • CD276 [B7-H3]
  • Camelid single domain antibody (sdAb)
  • Gene delivery
  • Human epithelial ovarian cancer cell (SKOV3.ip1)
  • Ovarian Cancer (OvCa) xenograft mouse model

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