Airway gene transfer in a non-human primate: lentiviral gene expression in marmoset lungs

Sci Rep. 2013:3:1287. doi: 10.1038/srep01287.

Abstract

Genetic therapies for cystic fibrosis (CF) must be assessed for safety and efficacy, so testing in a non-human primate (NHP) model is invaluable. In this pilot study we determined if the conducting airways of marmosets (n = 2) could be transduced using an airway pre-treatment followed by an intratracheal bolus dose of a VSV-G pseudotyped HIV-1 based lentiviral (LV) vector (LacZ reporter). LacZ gene expression (X-gal) was assessed after 7 days and found primarily in conducting airway epithelia as well as in alveolar regions. The LacZ gene was not detected in liver or spleen via qPCR. Vector p24 protein bio-distribution into blood was transient. Dosing was well tolerated. This preliminary study confirmed the transducibility of CF-relevant airway cell types. The marmoset is a promising NHP model for testing and translating genetic treatments for CF airway disease towards clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Callithrix / virology*
  • Cystic Fibrosis / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Female
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Vectors
  • Lac Operon / genetics*
  • Lentivirus / genetics*
  • Lung / metabolism
  • Lung / virology
  • Male
  • Pilot Projects
  • Transduction, Genetic / methods*

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator