Assessment of F/HN-Pseudotyped Lentivirus as a Clinically Relevant Vector for Lung Gene Therapy

Uta Griesenbach, Makoto Inoue, Cuixiang Meng, Raymond Farley, Mario Chan, Nikki K. Newman, Andrea Brum, Jun You, Angela Kerton, Amelia Shoemark, A. Christopher Boyd, Jane C. Davies, Tracy E. Higgins, Deborah R. Gill, Stephen C. Hyde, J. Alastair Innes, David J. Porteous, Mamoru Hasegawa, Eric W. F. W. Alton

Research output: Contribution to journalArticlepeer-review


Rationale. Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. Objectives: To place this vector onto a translational pathway to the clinic by addressing some key milestones that have to be achieved.

Methods: F/HN-SIV transduction efficiency, duration of expression, and toxicity were assessed in mice. In addition, F/HN-SIV was assessed in differentiated human air liquid interface cultures, primary human nasal epithelial cells, and human and sheep lung slices.

Measurements and Main Results: A single dose produces lung expression for the lifetime of the mouse (similar to 2 yr). Only brief contact time is needed to achieve transduction. Repeated daily administration leads to a dose-related increase in gene expression. Repeated monthly administration to mouse lower airways is feasible without loss of gene expression. There is no evidence of chronic toxicity during a 2-year study period. F/HN-SIV leads to persistent gene expression in human differentiated airway cultures and human lung slices and transduces freshly obtained primary human airway epithelial cells.

Conclusions: The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene therapy for several diseases including CF. We are now undertaking the necessary refinements to progress this vector into clinical trials.

Original languageEnglish
Pages (from-to)846-856
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number9
Publication statusPublished - 1 Nov 2012


  • cystic fibrosis
  • gene transfer
  • gene therapy
  • lentivirus
  • lung

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