Abstract
Traditional gene therapy vectors have demonstrated limited utility for treatment of chronic lung diseases such as cystic fibrosis (CF). Herein we describe a vector based on a Filovirus envelope protein-pseudotyped HIV vector, which we chose after systematically evaluating multiple strategies. The vector efficiently transduces intact airway epithelium from the apical surface, as demonstrated in both in vitro and in vivo model systems. This shows the potential of pseudotyping in expanding the utility of lentiviral vectors. Pseudotyped lentiviral vectors may hold promise for the treatment of CF.
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Acknowledgements
The authors thank Dr. Inder Verma for providing pCMVΔR8.2, pHR′LacZ, and the VSV-G envelope expressor, Dr. Paul Bates for providing the EboZ and EboR envelope plasmids as well as antibodies against the Ebola envelope glycoprotein, Dr. Eric Hunter for providing the BH-RCANsHA envelope plasmid, Dr. Jacob Reizer for providing the Mokola envelope plasmid, Dr. Eric Cohen for providing the SVCMV in plasmid and the amphotropic MuLV envelope, Dr. Christian Moser for insightful discussion, and Dr. John Tazelaar for assistance with tissue processing and microscopy. G.P.K. is the recipient of a fellowship from the Medical Research Council of Canada. This work was funded by grants from the National Institutes of Health (DK47757-08), the CF Foundation, and Genovo, Inc., a biotechnology company Dr. Wilson founded and in which he has equity.
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Kobinger, G., Weiner, D., Yu, QC. et al. Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo. Nat Biotechnol 19, 225–230 (2001). https://doi.org/10.1038/85664
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DOI: https://doi.org/10.1038/85664
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