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Improved DNA: liposome complexes for increased systemic delivery and gene expression

Nature Biotechnology volume 15, pages 647–652 (1997)Cite this article

Abstract

To increase cationic liposome-mediated intravenous DNA delivery extruded DOTAPicholesterol lipo-somes were used to form complexes with DNA, resulting in enhanced expression of the chloramphenicol acetyltransferase gene in most tissues examined. The DNA:liposome ratio, and mild sonication, heating, and extrusion steps used for liposome preparation were crucial for improved systemic delivery. Size fractionation studies showed that maximal gene expression was produced by a homogeneous population of DNA:liposome complexes between 200 to 450 nm in size. Cryo-electron microscopy examination demonstrates that the DNA:liposome complexes have a novel morphology, and that the DNA is condensed on the interior of invaginated liposomes between two lipid bilayers. This structure could account for the high efficiency of gene delivery in vivo and for the broad tissue distribution of the DNA:liposome complexes. Ligands can be placed on the outside of this structure to provide for targeted gene delivery.

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Author information

Authors and Affiliations

  1. NCI-FCRDC, ABL-Basic Research Program, P.O. Box B, Boyles Street, Bldg. 535, Rm. 226A, Frederick, MD, 21702-1201

    Nancy Smyth Templeton & George N. Pavlakis

  2. Liposome Consultations, 7512 Birkdale Drive, Newark, CA, 94560

    Danilo D. Lasic

  3. EM Unit, Department of Pathology, University of Limburg, Maastricht, The Netherlands

    Peter M. Frederik

  4. DCRT/LSB, National Institutes of Health, Bldg. 12A, Room 2041, 12 South Drive, MSC 5626, Bethesda, MD, 20892

    Helmut H. Strey

  5. Laboratory of Pathology, National Institutes of Health, Bldg. 10, Rm. 2A33,10 Center Drive MSC 1500, Bethesda, MD, 20892

    David D. Roberts

Authors
  1. Nancy Smyth Templeton
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  2. Danilo D. Lasic
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  3. Peter M. Frederik
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  4. Helmut H. Strey
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  6. George N. Pavlakis
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Correspondence to Nancy Smyth Templeton.

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Templeton, N., Lasic, D., Frederik, P. et al. Improved DNA: liposome complexes for increased systemic delivery and gene expression. Nat Biotechnol 15, 647–652 (1997). https://doi.org/10.1038/nbt0797-647

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