Systemic Gene Therapy: Biodistribution and Long-Term Expression of a Transgene in Mice

We have investigated the in vivo efficacy of a systemic gene transfer method, which combines a liposomal delivery system (DLS liposomes) with episomally replicative DNA plasmids to effect long-term expression of a transgene in cells. A single i.v. injection of a plasmid DNA vector containing the luc...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-10, Vol.92 (21), p.9742-9746
Main Authors: Thierry, Alain R., Lunardi-Iskandar, Yanto, Bryant, Joseph L., Rabinovich, Peter, Gallo, Robert C., Mahan, Lawrence C.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Bone marrow cells
Cyclic N-Oxides - administration & dosage
Deoxyribonucleic acid
DNA
DNA, Recombinant - administration & dosage
Dose-Response Relationship, Drug
Drug Administration Routes
Drug Carriers - administration & dosage
Female
Gene therapy
Gene Transfer Techniques
Genetic Therapy - methods
Genetic Vectors
Growth
Immunohistochemistry
Liposomes
Liposomes - administration & dosage
Liver
Luciferases - genetics
Lungs
Mice
Mice, Inbred BALB C
Mice, Transgenic
Molecular Sequence Data
Plasmids
Plasmids - genetics
Polymerase chain reaction
Rodents
Spleen
Tissue Distribution
Transgenes
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Summary:We have investigated the in vivo efficacy of a systemic gene transfer method, which combines a liposomal delivery system (DLS liposomes) with episomally replicative DNA plasmids to effect long-term expression of a transgene in cells. A single i.v. injection of a plasmid DNA vector containing the luciferase gene as a marker was administered with the DLS liposomes in BALB/c mice. The luciferase gene and its product were found in all mouse tissues tested as determined by PCR analysis and immunohistochemistry. Luciferase activity was also detected in all tissues tested and was present in lung, liver, spleen, and heart up to 3 months postinjection. In contrast to the nonepisomal vectors tested (pRSV-luc and pCMVintlux), human papovavirus (BKV)-derived episomal vectors showed long-term transgene expression. We found that these episomal vectors replicated extrachromosomally in lung 2 weeks postinjection. Results indicated that transgene expression in specific tissues depended on the promoter element used, DNA/liposome formulation, dose of DNA per injection, and route of administration.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.21.9742