title: Airway gene transfer in a non-human primate: lentiviral gene expression in marmoset lungs.
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.
authors: Respiratory and Sleep Medicine, Women's and Children's Health Network, North Adelaide, South Australia, Australia.
authors: N
authors: N
authors: Farrow
authors: D
authors: D
authors: Miller
authors: P
authors: P
authors: Cmielewski
authors: M
authors: M
authors: Donnelley
authors: R
authors: R
authors: Bright
authors: D W
authors: DW
authors: Parsons
mesh_terms: D000818:Animals; D002144:Callithrix / Q000821:virology*; D003550:Cystic Fibrosis / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007763:Lac Operon / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000821:virology; D008297:Male; D010865:Pilot Projects; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator