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Multifunctional nanorods for gene delivery

Abstract

The goal of gene therapy is to introduce foreign genes into somatic cells to supplement defective genes or provide additional biological functions1,2, and can be achieved using either viral or synthetic non-viral delivery systems. Compared with viral vectors, synthetic gene-delivery systems, such as liposomes and polymers, offer several advantages including ease of production and reduced risk of cytotoxicity and immunogenicity3,4, but their use has been limited by the relatively low transfection efficiency. This problem mainly stems from the difficulty in controlling their properties at the nanoscale. Synthetic inorganic gene carriers have received limited attention in the gene-therapy community, the only notable example being gold nanoparticles with surface-immobilized DNA applied to intradermal genetic immunization by particle bombardment5. Here we present a non-viral gene-delivery system based on multisegment bimetallic nanorods that can simultaneously bind compacted DNA plasmids and targeting ligands in a spatially defined manner. This approach allows precise control of composition, size and multifunctionality of the gene-delivery system. Transfection experiments performed in vitro and in vivo provide promising results that suggest potential in genetic vaccination applications.

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Figure 1: Spatially selective binding of DNA plasmids and transferrin to multicomponent nanorods.
Figure 2: Stacked laser scanning confocal microscope images of transfected cells.
Figure 3: Uptake of nanorods observed by SEM and TEM analysis.
Figure 4: Results of transfection experiments.

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Acknowledgements

This work was supported by the Defense Advanced Research Projects Agency (DARPA) and Air Force Office of Scientific Research (AFOSR, under grant number F49620-02-1-0307).

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Correspondence to Kam W. Leong.

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The authors declare no competing financial interests.

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Salem, A., Searson, P. & Leong, K. Multifunctional nanorods for gene delivery. Nature Mater 2, 668–671 (2003). https://doi.org/10.1038/nmat974

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