Controlled gene delivery by DNA-gelatin nanospheres

Vu L. Truong-Le, J. Thomas August, Kam W. Leong

Research output: Contribution to journalArticle

Abstract

A novel system for gene delivery, based on the use of DNA-gelatin nanoparticles (nanospheres) formed by salt-induced complex coacervation of gelatin and plasmid DNA, has been developed. These particles were spherical, with a size range of 200-700 nm, contained 25-30% (w/w) DNA, and were stabilized by cross-linking of gelatin. As a consequence of being controlled by the cross-linking density of the gelatin matrix, the average release rate of DNA from nanospheres synthesized under standard conditions was 2.2%/day in serum. Nanosphere DNA incubated in bovine serum was more resistant to nuclease digestion than was naked DNA. Various bioactive agents could be encapsulated in the nanospheres by ionic interaction with the matrix components, physical entrapment, or covalent conjugation. Transfection of cultured cells with a luciferase plasmid was enhanced by conjugating human transferrin onto the nanosphere and coencapsulating the endolysolytic agent chloroquine. Under our experimental conditions, gene expression in mice subsequent to intramuscular injection of nanospheres containing 1 μg of a β-galactosidase plasmid was greater and more prolonged than was observed after injection of an equal amount of naked DNA or DNA complexed with Lipofectamine.

Original languageEnglish (US)
Pages (from-to)1709-1717
Number of pages9
JournalHuman gene therapy
Volume9
Issue number12
DOIs
StatePublished - Aug 10 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Truong-Le, V. L., Thomas August, J., & Leong, K. W. (1998). Controlled gene delivery by DNA-gelatin nanospheres. Human gene therapy, 9(12), 1709-1717. https://doi.org/10.1089/hum.1998.9.12-1709