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Redirecting adenovirus to pulmonary endothelium by cationic liposomes

Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver...

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Autores principales: Ma, Z, Mi, Z, Wilson, A, Alber, S, Robbins, PD, Watkins, S, Pitt, B, Li, S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091708/
https://www.ncbi.nlm.nih.gov/pubmed/11859420
http://dx.doi.org/10.1038/sj.gt.3301636
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author Ma, Z
Mi, Z
Wilson, A
Alber, S
Robbins, PD
Watkins, S
Pitt, B
Li, S
author_facet Ma, Z
Mi, Z
Wilson, A
Alber, S
Robbins, PD
Watkins, S
Pitt, B
Li, S
author_sort Ma, Z
collection PubMed
description Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have proven to be limited for pulmonary gene transfer with respect to efficiency, in part because of difficulty in assuring significant residence time in the lung and/or paucity of receptors for adenovirus on the endothelium. A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. In this study, we report that pulmonary gene transfer by Ad vectors can also be improved significantly via the use of cationic liposomes. Preinjection of cationic liposomes followed by adenovirus led to a significant increase in the level of gene expression in the lung. The improvement in pulmonary gene transfer was associated with a decrease in the level of gene expression in the liver. Gene expression in the lung lasted for up to 2 weeks. This protocol, together with genetic modification of adenovirus, may prove to be useful for pulmonary gene transfer for the treatment of pulmonary diseases. This method may also be extended to pulmonary gene transfer using other types of viral vectors via vascular route.
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spelling pubmed-70917082020-03-24 Redirecting adenovirus to pulmonary endothelium by cationic liposomes Ma, Z Mi, Z Wilson, A Alber, S Robbins, PD Watkins, S Pitt, B Li, S Gene Ther Article Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have proven to be limited for pulmonary gene transfer with respect to efficiency, in part because of difficulty in assuring significant residence time in the lung and/or paucity of receptors for adenovirus on the endothelium. A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. In this study, we report that pulmonary gene transfer by Ad vectors can also be improved significantly via the use of cationic liposomes. Preinjection of cationic liposomes followed by adenovirus led to a significant increase in the level of gene expression in the lung. The improvement in pulmonary gene transfer was associated with a decrease in the level of gene expression in the liver. Gene expression in the lung lasted for up to 2 weeks. This protocol, together with genetic modification of adenovirus, may prove to be useful for pulmonary gene transfer for the treatment of pulmonary diseases. This method may also be extended to pulmonary gene transfer using other types of viral vectors via vascular route. Nature Publishing Group UK 2002-02-22 2002 /pmc/articles/PMC7091708/ /pubmed/11859420 http://dx.doi.org/10.1038/sj.gt.3301636 Text en © Macmillan Publishers Limited 2002 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Ma, Z
Mi, Z
Wilson, A
Alber, S
Robbins, PD
Watkins, S
Pitt, B
Li, S
Redirecting adenovirus to pulmonary endothelium by cationic liposomes
title Redirecting adenovirus to pulmonary endothelium by cationic liposomes
title_full Redirecting adenovirus to pulmonary endothelium by cationic liposomes
title_fullStr Redirecting adenovirus to pulmonary endothelium by cationic liposomes
title_full_unstemmed Redirecting adenovirus to pulmonary endothelium by cationic liposomes
title_short Redirecting adenovirus to pulmonary endothelium by cationic liposomes
title_sort redirecting adenovirus to pulmonary endothelium by cationic liposomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091708/
https://www.ncbi.nlm.nih.gov/pubmed/11859420
http://dx.doi.org/10.1038/sj.gt.3301636
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