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Improved Dna - Liposome Complexes For Increased Systemic Delivery and Gene Expression

  1. Author:
    Templeton, N. S.
    Lasic, D. D.
    Frederik, P. M.
    Strey, H. H.
    Roberts, D. D.
    Pavlakis, G. N.

  2. Author Address

    Templeton NS NCI FREDERICK CANC RES & DEV CTR ABL BASIC RES PROGRAM POB B BOYLES ST BLDG 535 RM 226A FREDERICK, MD 21702 USA LIPSOME CONSULTAT NEWARK, CA 94560 USA UNIV LIMBURG DEPT PATHOL NL-6200 MD MAASTRICHT NETHERLANDS NIH DCRT LSB BETHESDA, MD 20892 USA NIH PATHOL LAB BETHESDA, MD 20892 USA
    1. Year: 1997
  2. Journal: Nature Biotechnology
    1. 15
    2. 7
    3. Pages: 647-652
  4. Type of Article: Article
  1. Abstract:

    To increase cationic liposome-mediated intravenous DNA delivery extruded DOTAP:cholesterol liposomes 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. [References: 30]

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