Silica cloaking of adenovirus enhances gene delivery while reducing immunogenicity

Ajay A. Sapre, Gen Yong, Ya san Yeh, Laura E. Ruff, Justin S. Plaut, Zeynep Sayar, Anupriya Agarwal, Jacqueline Martinez, Theresa N. Nguyen, Yu Tsueng Liu, Bradley T. Messmer, Sadik Esener, Jared Fischer

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Viral gene therapy is a means of delivering genes to replace malfunctioning ones, to kill cancer cells, or to correct genetic mutations. This technology is emerging as a powerful clinical tool; however, it is still limited by viral tropism, uptake and clearance by the liver, and most importantly an immune response. To overcome these challenges, we sought to merge the robustness of viral gene expression and the versatility of nanoparticle technology. Here, we describe a method for cloaking adenovirus (Ad) in silica (SiAd) as a nanoparticle formulation that significantly enhances transduction. Intratumoral injections in human glioma xenografts revealed SiAd expressing luciferase improved tumor transduction while reducing liver uptake. In immune-competent mice SiAd induced no inflammatory cytokines and reduced production of neutralizing antibodies. Finally, SiAd expressing TNF-related apoptosis-inducing ligand inhibited tumor growth of glioma xenografts. These results reveal that silica cloaking of Ad can enhance viral gene delivery while reducing immunogenicity.

Original languageEnglish (US)
Pages (from-to)48-59
Number of pages12
JournalJournal of Controlled Release
Volume297
DOIs
StatePublished - Mar 10 2019

Keywords

  • Adenovirus
  • Gene delivery
  • Gene therapy
  • Nanoparticle
  • Silica

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Sapre, A. A., Yong, G., Yeh, Y. S., Ruff, L. E., Plaut, J. S., Sayar, Z., Agarwal, A., Martinez, J., Nguyen, T. N., Liu, Y. T., Messmer, B. T., Esener, S., & Fischer, J. (2019). Silica cloaking of adenovirus enhances gene delivery while reducing immunogenicity. Journal of Controlled Release, 297, 48-59. https://doi.org/10.1016/j.jconrel.2019.01.034