Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA
RNA interference (RNAi) may provide a therapeutic solution to many pulmonary epithelium diseases. However, the main barrier to the clinical use of RNAi remains the lack of efficient delivery vectors. Research has mainly concentrated on the intranasal route of delivery of short interfering RNA (siRNA...
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doaj-581bb66844fd485abb14d9aca2d8362b2020-11-24T23:08:04ZengElsevierMolecular Therapy: Nucleic Acids2162-25312013-01-012C10.1038/mtna.2013.22Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNAJana McCaskill0Richa Singhania1Melinda Burgess2Rachel Allavena3Sherry Wu4Antje Blumenthal5Nigel AJ McMillan6Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USARNA interference (RNAi) may provide a therapeutic solution to many pulmonary epithelium diseases. However, the main barrier to the clinical use of RNAi remains the lack of efficient delivery vectors. Research has mainly concentrated on the intranasal route of delivery of short interfering RNA (siRNA) effector molecules for the treatment of respiratory diseases. However, this may be complicated in a diseased state due to the increased fluid production and tissue remodeling. Therefore, we investigated our hydration of a freeze-dried matrix (HFDM) formulated liposomes for systemic delivery to the lung epithelium. Here, we show that 45 ± 2% of epithelial murine lung cells receive siRNA delivery upon intravenous (IV) liposomal administration. Furthermore, we demonstrate that liposomal siRNA delivery resulted in targeted gene and protein knockdown throughout the lung, including lung epithelium. Taken together, this is the first description of lung epithelial delivery via cationic liposomes, and provides a proof of concept for the use of IV liposomal RNAi delivery to specifically knockdown targeted genes in the respiratory system. This approach may provide an attractive alternate therapeutic delivery strategy for the treatment of lung epithelium diseases.http://www.sciencedirect.com/science/article/pii/S216225311630155Xendothelialepithelialin vivolungsiRNAstealth liposome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jana McCaskill Richa Singhania Melinda Burgess Rachel Allavena Sherry Wu Antje Blumenthal Nigel AJ McMillan |
spellingShingle |
Jana McCaskill Richa Singhania Melinda Burgess Rachel Allavena Sherry Wu Antje Blumenthal Nigel AJ McMillan Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA Molecular Therapy: Nucleic Acids endothelial epithelial in vivo lung siRNA stealth liposome |
author_facet |
Jana McCaskill Richa Singhania Melinda Burgess Rachel Allavena Sherry Wu Antje Blumenthal Nigel AJ McMillan |
author_sort |
Jana McCaskill |
title |
Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA |
title_short |
Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA |
title_full |
Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA |
title_fullStr |
Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA |
title_full_unstemmed |
Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA |
title_sort |
efficient biodistribution and gene silencing in the lung epithelium via intravenous liposomal delivery of sirna |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2013-01-01 |
description |
RNA interference (RNAi) may provide a therapeutic solution to many pulmonary epithelium diseases. However, the main barrier to the clinical use of RNAi remains the lack of efficient delivery vectors. Research has mainly concentrated on the intranasal route of delivery of short interfering RNA (siRNA) effector molecules for the treatment of respiratory diseases. However, this may be complicated in a diseased state due to the increased fluid production and tissue remodeling. Therefore, we investigated our hydration of a freeze-dried matrix (HFDM) formulated liposomes for systemic delivery to the lung epithelium. Here, we show that 45 ± 2% of epithelial murine lung cells receive siRNA delivery upon intravenous (IV) liposomal administration. Furthermore, we demonstrate that liposomal siRNA delivery resulted in targeted gene and protein knockdown throughout the lung, including lung epithelium. Taken together, this is the first description of lung epithelial delivery via cationic liposomes, and provides a proof of concept for the use of IV liposomal RNAi delivery to specifically knockdown targeted genes in the respiratory system. This approach may provide an attractive alternate therapeutic delivery strategy for the treatment of lung epithelium diseases. |
topic |
endothelial epithelial in vivo lung siRNA stealth liposome |
url |
http://www.sciencedirect.com/science/article/pii/S216225311630155X |
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