Effect of co-lipids in enhancing cationic lipid-mediated gene transfer in vitro and in vivo (original) (raw)

Gene Therapy volume 4, pages 716–725 (1997)Cite this article

Abstract

Complexes of DNA and cationic lipids are promising vectors for gene transfer. Most cationic lipid formulations contain both a cationic component and a neutral co-lipid. We found that the co-lipid could influence DNA uptake in COS-1 cells, but processes subsequent to uptake were even more important in determining gene expression. We compared dioleoylphosphatidylethanolamine (DOPE) and structural analogs of DOPE combined with cationic lipids and found that DNA uptake and transgene expression did not always correlate. Transgene expression was dependent on DNA uptake into the cell, on entry of DNA into the cytoplasm, and on release of DNA from the lipid complex. We found that some co-lipids had a greater effect on DNA uptake, whereas others had a greater effect on steps subsequent to entry. Based on those results, we tested the hypothesis that co-lipids conferring different properties could be combined to enhance gene transfer. The results showed that a combination of co-lipids had a synergistic effect on expression. We also found that structural analogs of DOPE were more effective than DOPE in enhancing gene transfer to mature human airway epithelia studied in vitro and to mouse lung studied in vivo. These data provide insight into the mechanism by which co-lipids influence cationic lipid-mediated gene transfer and show that optimization of the effects of co-lipids can enhance gene transfer both in vitro and in vivo.

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Authors and Affiliations

  1. Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA, USA
    A Fasbender, TO Moninger, T Grunst & MJ Welsh
  2. Genzyme Corporation, Framingham, MA, USA
    J Marshall & S Cheng

Authors

  1. A Fasbender
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  2. J Marshall
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  3. TO Moninger
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  4. T Grunst
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  5. S Cheng
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  6. MJ Welsh
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Fasbender, A., Marshall, J., Moninger, T. et al. Effect of co-lipids in enhancing cationic lipid-mediated gene transfer in vitro and in vivo.Gene Ther 4, 716–725 (1997). https://doi.org/10.1038/sj.gt.3300459

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