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Robust and prolonged gene expression from injectable polymeric implants

Gene Therapy volume 9, pages 1230–1237 (2002)Cite this article

Abstract

We introduce an injectable system for the formation of a biodegradable DNA-containing implant that releases DNA over a 2-month period to provide a robust and prolonged gene expression at the site. Sustained delivery of the appropriate plasmid DNA resulted in sustained expression of luciferase, the persistent appearance of secreted alkaline phosphatase in the serum and small blood vessel formation in the vicinity of the implant from the delivery of the development endothelial locus-1 gene. Local expression of development endothelial locus-1 protein promotes the development of blood vessels to meet the metabolic demands of new tissue and is a paradigm for the delivery of other growth factors that act locally to aid tissue regeneration. This delivery system involves simple preparation procedures and can be injected directly into the site, hence should be a useful approach to plasmid-based gene transfer for vaccination and tissue engineering.

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Acknowledgements

We thank Yael Eliaz for assistance with the statistical analysis, Michael Coleman and Liz Wilson for helpful comments on the manuscript and Edward Dy for technical assistance. We thank Valentis Inc. (Burlingame, CA, USA) for the gift of the plasmid DNA used in this research. We gratefully acknowledge financial support from NIH DK 46052 and the State of California Tobacco-Related Disease Research Program 8IT-0138. Dr Szoka has a financial interest in and serves as a consultant to Valentis, a biotechnology company developing gene medicines. We also thank Donald McDonald for access to the vibratome used to section the implants.

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  1. R E Eliaz

    Present address: Alza Corporation, 1900 Charleston Road, Mountain View, 94043, CA, USA

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  1. Department of Biopharmaceutical Sciences and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA

    R E Eliaz & F C Szoka Jr.

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  1. R E Eliaz
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  2. F C Szoka Jr.
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Eliaz, R., Szoka, F. Robust and prolonged gene expression from injectable polymeric implants. Gene Ther 9, 1230–1237 (2002). https://doi.org/10.1038/sj.gt.3301786

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