Using the nose as a factory to secrete proteins into the lungs or circulation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Targeting of the nasal epithelium for sustained therapeutic protein secretion represents a potential non-invasive lentiviral vector application strategy. Using reporter imaging, molecular, and radiopharmaceutical tracing methods in mice, we have developed an intranasal (nose-only) dosing strategy with a Sendai-virus envelope glycoprotein pseudotyped lentiviral vector (rSIV.F/HN). Using multiple (up to 10) small volume (5 μL) intranasal bolus applications, technetium radiotracer showed >90% liquid retention in the murine head and <1% in the lung. Following vector administration, transgene expression was dose-related in the nose with minimal lung expression. No acute nasal toxicity was associated with nose-only delivery. Next, we compared levels of a secreted protein, Gaussia luciferase (Gluc), in the airways and serum after nose-only and intravenous administration of rSIV.F/HN-Gluc (2e8 TU/mouse). Gluc expression in the nose and lungs was higher following nose-only versus intravenous administration. Serum levels were similar after either route of administration. Finally, nose-only delivery of rSIV.F/HN encoding GM-CSF, led to sufficient lung levels of this therapeutic protein to correct disease biomarkers in a mouse model of pulmonary alveolar proteinosis. We conclude that non-invasive administration of a lentiviral vector to the nasal epithelium provides a safe and convenient route for secreted protein production and is readily translatable into humans.
Date Issued
2026-06-11
Date Acceptance
2026-04-03
Citation
Molecular Therapy Advances, 2026, 34 (2)
ISSN
3117-387X
Publisher
Elsevier BV
Journal / Book Title
Molecular Therapy Advances
Volume
34
Issue
2
Copyright Statement
© 2026 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.omta.2026.201733
Publication Status
Published
Article Number
201733
Date Publish Online
2026-04-06