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@article{Sinadinos:2026:10.1016/j.omta.2026.201733,
author = {Sinadinos, A and Bell, R and Juarez-Molina, CI and Meng, C and Castells, E and Viegas, MA and Gill, DR and Hyde, SC and Griesenbach, U and Alton, EWFW},
doi = {10.1016/j.omta.2026.201733},
journal = {Molecular Therapy Advances},
title = {Using the nose as a factory to secrete proteins into the lungs or circulation},
url = {http://dx.doi.org/10.1016/j.omta.2026.201733},
year = {2026}
}
TY - JOUR
AB - 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.
AU - Sinadinos,A
AU - Bell,R
AU - Juarez-Molina,CI
AU - Meng,C
AU - Castells,E
AU - Viegas,MA
AU - Gill,DR
AU - Hyde,SC
AU - Griesenbach,U
AU - Alton,EWFW
DO - 10.1016/j.omta.2026.201733
PY - 2026///
SN - 3117-387X
TI - Using the nose as a factory to secrete proteins into the lungs or circulation
T2 - Molecular Therapy Advances
UR - http://dx.doi.org/10.1016/j.omta.2026.201733
UR - https://doi.org/10.1016/j.omta.2026.201733
ER -