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Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration

Nature Medicine volume 5, pages 753–759 (1999)Cite this article

Abstract

The inability to deliver growth factors locally in a transient but sustained manner is a substantial barrier to tissue regeneration. Systems capable of localized plasmid gene delivery for prolonged times may offer lower toxicity and should be well-suited for growth factor therapeutics. We investigated the potency of plasmid gene delivery from genes physically entrapped in a polymer matrix (gene activated matrix) using bone regeneration as the endpoint in vivo. Implantation of gene activated matrices at sites of bone injury was associated with retention and expression of plasmid DNA for at least 6 weeks, and with the induction of centimeters of normal new bone in a stable, reproducible, dose- and time-dependent manner.

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Figure 1: Direct in vivo plasmid gene transfer.
Figure 2: Bone formation dose-response: part 1.
Figure 3: Bone formation dose–response: part 2.
Figure 4: Histology.
Figure 5: Histology and immunohistochemistry of cartilage callus.
Figure 6: Local recombinant protein and plasmid gene delivery in tissue repair and regeneration.

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Acknowledgements

The authors acknowledge the assistance of M. Wagner (illustrations) and J. Baker, C. Debano, D. Kayner, K. Sweet, and R. Taylor (canine models and tissue preparation). J.B. thanks M. Young, Z. Shaked, D. Mooney, B. Abbott, and A. Baird for discussions. Thanks to P. Hoyle for advice and support. These studies were supported by a grant from NIH and by a Sponsored Research Agreement from Selective Genetics to the University of Michigan.

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  1. Jeffrey Bonadio

    Present address: Selective Genetics, 11035 Roselle Street, San Diego, California, 92121, USA

Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109-0417, Michigan, USA

    Jeffrey Bonadio & Elizabeth Smiley

  2. Orthopaedic Research Laboratories, University of Michigan Medical School, Ann Arbor, 48109-0486, Michigan, USA

    Pravin Patil & Steven Goldstein

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  1. Jeffrey Bonadio
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Correspondence to Jeffrey Bonadio.

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Bonadio, J., Smiley, E., Patil, P. et al. Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration. Nat Med 5, 753–759 (1999). https://doi.org/10.1038/10473

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