Multifunctional nanorods for gene delivery (original) (raw)

Nature Materials volume 2, pages 668–671 (2003)Cite this article

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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References

  1. Luo, D. & Saltzman, W.M. Synthetic DNA delivery systems. Nature Biotechnol. 18, 33–37 (2000).
    Article CAS Google Scholar
  2. Roy, K., Mao, H.Q., Huang, S.K. & Leong, K.W. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nature Med. 5, 387–391 (1999).
    Article CAS Google Scholar
  3. Carter, P.J. & Samulski, R.J. Adeno-associated viral vectors as gene delivery vehicles (review). Int. J. Mol. Med. 6, 17–27 (2000).
    CAS Google Scholar
  4. Pouton, C.W. & Seymour, L.W. Key issues in non-viral gene delivery. Adv. Drug Deliver. Rev. 46, 187–203 (2001).
    Article CAS Google Scholar
  5. Yang, N.S. & Sun, W.H. Gene gun and other nonviral approaches for cancer gene-therapy. Nature Med. 1, 481–483 (1995).
    Article CAS Google Scholar
  6. Martin, C.R. Nanomaterials - a membrane-based synthetic approach. Science 266, 1961–1966 (1994).
    Article CAS Google Scholar
  7. Whitney, T.M., Jiang, J.S., Searson, P.C. & Chien, C.L. Fabrication and magnetic-properties of arrays of metallic nanowires. Science 261, 1316–1319 (1993).
    Article CAS Google Scholar
  8. Sun, L., Searson, P.C. & Chien, C.L. Magnetic anisotropy in prismatic nickel nanowires. Appl. Phys. Lett. 79, 4429–4431 (2001).
    Article CAS Google Scholar
  9. Wagner, E., Curiel, D. & Cotten, M. Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis. Adv. Drug Deliver. Rev. 14, 113–135 (1994).
    Article CAS Google Scholar
  10. Laibinis, P.E., Hickman, J.J., Wrighton, M.S. & Whitesides, G.M. Orthogonal self-assembled monolayers - alkanethiols on gold and alkane carboxylic-acids on alumina. Science 245, 845–847 (1989).
    Article CAS Google Scholar
  11. Roy, I., Mitra, S., Maitra, A. & Mozumdar, S. Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery. Int. J. Pharm. 250, 25–33 (2003).
    Article CAS Google Scholar

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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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Authors and Affiliations

  1. Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, 21205, Maryland, USA
    Aliasger K. Salem & Kam W. Leong
  2. Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, 21218, Maryland, USA
    Aliasger K. Salem & Peter C. Searson

Authors

  1. Aliasger K. Salem
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  2. Peter C. Searson
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  3. Kam W. Leong
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Corresponding author

Correspondence toKam 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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