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Nucleic Acids Research, Vol 27, Issue 20 4071-4076, Copyright © 1999 by Oxford University Press

ARTICLES

Lipophilic pro-oligonucleotides are rapidly and efficiently internalized in HeLa cells

E Vives, C Dell'Aquila, JC Bologna, F Morvan, B Rayner and JL Imbach
Laboratoire de Chimie Bio-Organique, Universite Montpellier II, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France.

Model t-Bu-SATE pro-dodecathymidines labeled with fluorescein and exhibiting various lipophilicities were evaluated for their uptake by cells in culture. Pro-oligonucleotides with appropriate lipophilicity were found to permeate across the HeLa cell membrane much more extensively than the control phosphorothioate oligo or than the hydrophilic pro-oligos. Fluorescence patterns of internalization were consistent with a diffusion mechanism resulting in the appearance of a uniform cytoplasmic distribution and nuclear accumulation, as confirmed by confocal microscopy.
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