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A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wheeler, Carl J. Felgner, Philip L. Tsai, Y. J. Marshall, John Sukhu, Loretta Doh, S. G. Hartikka, Jukka Nietupski, Jennifer B. Manthorpe, Marston Nichols, Maxine B. Plewe, Michael B. Liang, Xiangyang Norman, Jessica A. Smith, Amanda Cheng, Seng H. |
| Copyright Year | 1996 |
| Abstract | Effective gene therapy for lung tissue requires the use of efficient vehicles to deliver the gene of interest into lung cells. When plasmid DNA encoding chloramphenicol acetyltransferase (CAT) was administered intranasally to BALB/c mice without carrier lipids, CAT activity was detected in mouse lung extracts. Plasmid DNA delivered with optimally formulated commercially available transfection reagents expressed up to 10-fold more CAT activity in lung than observed with naked DNA alone. Liposome formulations consisting of (+/-)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis (dodecyloxy)-1-propanaminium bromide (GAP-DLRIE) plus the neutral colipid dioleoylphosphatidylethanolamine (DOPE) enhanced CAT expression by more than 100-fold relative to plasmid DNA alone. A single administration of GAP-DLRIE liposome-CAT DNA complexes to mouse lung elicited peak expression at days 1-4 posttransfection, followed by a gradual return to baseline by day 21 postadministration. Readministration of GAP-DLRIE liposome CAT complexes at day 21 led to another transient peak of reporter gene expression. Histological examination of lungs treated with GAP-DLRIE complexed beta-galactosidase DNA revealed that alveolar epithelial cells were the primary locus of expression and that up to 1% of all alveoli contained epithelial cells expressing the transgene. |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/93/21/11454.full.pdf |
| PubMed reference number | 8876156v1 |
| Volume Number | 93 |
| Issue Number | 21 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 2,4-dinitrophenyl-dioleoylphosphatidylethanolamine Acyltransferase Alveolus Chloramphenicol O-Acetyltransferase Contain (action) Drug vehicle Galactosidase Gene Expression Greater Than Liposomes Reagents Retreatments Structure of parenchyma of lung beta-Galactosidase dioleoyl phosphatidylethanolamine methscopolamine bromide |
| Content Type | Text |
| Resource Type | Article |
