@article{376abd9a8c754aaca6a8bafd0f9969c1,
title = "A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency",
abstract = "Surfactant protein B (SP-B) deficiency is an autosomal recessive disorder that impairs surfactant homeostasis and manifests as lethal respiratory distress. A compelling argument exists for gene therapy to treat this disease, as de novo protein synthesis of SP-B in alveolar type 2 epithelial cells is required for proper surfactant production. Here we report a rationally designed adeno-associated virus (AAV) 6 capsid that demonstrates efficiency in lung epithelial cell transduction based on imaging and flow cytometry analysis. Intratracheal administration of this vector delivering murine or human proSFTPB cDNA into SP-B deficient mice restores surfactant homeostasis, prevents lung injury, and improves lung physiology. Untreated SP-B deficient mice develop fatal respiratory distress within two days. Gene therapy results in an improvement in median survival to greater than 200 days. This vector also transduces human lung tissue, demonstrating its potential for clinical translation against this lethal disease.",
author = "Kang, {Martin H.} and {van Lieshout}, {Laura P.} and Liqun Xu and Domm, {Jakob M.} and Arul Vadivel and Laurent Renesme and Christian M{\"u}hlfeld and Maria Hurskainen and Ivana Mi{\v z}{\'i}kov{\'a} and Yanlong Pei and {van Vloten}, {Jacob P.} and Thomas, {Sylvia P.} and Claudia Milazzo and Chan{\`e}le Cyr-Depauw and Whitsett, {Jeffrey A.} and Nogee, {Lawrence M.} and Wootton, {Sarah K.} and Bernard Th{\'e}baud",
note = "Funding Information: This work was supported in part by funding from a CIHR Foundation Scheme Grant to B.T. (FDN-143316), a CHIR Project grant to S.K.W. and B.T. (420518), grants from The Lung Association–Ontario (34998) and The Mason Research Fund (44610) to S.K.W., NIH grant support to J.A.W. (U01HL134745 and U01HL148856), a European Respiratory Society Fellowship to L.R. (LTRF 2018), and Deutsche For-schungsgemeinschaft funding to I.M. The authors thank all the ACVS veterinary and technical staff at the University of Ottawa, and in particular Dr Mark Liepmann for the development of the respiratory distress scoring chart; Dr Greg Cron, for training of IVIS imaging; all the staff at the University of Ottawa Histology Core, especially Zaida Ticas and Sharlene Faulkes; Jeff McClintock at the CHEO Electron Microscope lab; and EORLA staff for the human fetal lung sample isolation, especially Janet Stinson and Korrine Hutt-Acres. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-17577-8",
language = "English (US)",
volume = "11",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}