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The role of cytoskeleton networks on lipid-mediated delivery of DNA

  • Author(s): Coppola, S
  • Cardarelli, F
  • Pozzi, D
  • Estrada, LC
  • Digman, MA
  • Gratton, E
  • Bifone, A
  • Marianecci, C
  • Caracciolo, G
  • et al.
Abstract

Background: Lipid-mediated delivery of DNA is hindered by extracellular and intracellular barriers that significantly reduce the transfection efficiency of synthetic nonviral vectors. Results: In this study we investigated the role of the actin and microtubule networks on the uptake and cytoplasmic transport of multicomponent cationic liposome-DNA complexes in CHO-K1 live cells by means of confocal laser scanning microscopy and 3D single particle tracking. Treatment with actin (latrunculin B)-and microtubule-disrupting (nocodazole) reagents indicated that intracellular trafficking of complexes predominantly involves microtubule-dependent active transport. We found that the actin network has a major effect on the initial uptake of complexes, while the microtubule network is mainly responsible for the subsequent active transportation to the lysosomes. Conclusion: Collectively, a strategy to improve the efficiency of lipid gene vectors can be formulated. We could find a lipid formulation that allows the nanoparticles to avoid the microtubule pathway to lysosomes. © 2013 Future Science Ltd.

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