Cancer gene therapy using plasmid DNA: Pharmacokinetic study of DNA following injection in mice

D. Lew, S. E. Parker, T. Latimer, A. M. Abai, A. Kuwahara-Rundell, S. G. Doh, Z. Y. Yang, D. Laface, S. H. Gromkowski, G. J. Nabel, M. Manthorpe, J. Norman

Research output: Contribution to journalArticlepeer-review

Abstract

The fate of plasmid DNA complexed with cationic lipids delivered intravenously in mice was evaluated at selected timepoints up to 6 months postinjection. Blood half-life and tissue distribution of plasmid DNA and potential expression in tissues were examined. Southern blot analyses of blood indicated that intact plasmid DNA was rapidly degraded, with a half-life of less than 5 min for intact plasmid, and was no longer detectable at 1 hr postinjection. Southern analyses of tissue demonstrated that intact DNA was differentially retained in the lung, spleen, liver, heart, kidney, marrow, and muscle up to 24 hr postinjection. After 7 days, no intact plasmid DNA was detectable by Southern blot analysis; however, the plasmid was detectable by the polymerase chain reaction (PCR) in all tissues examined at 7 and 28 days postinjection. At 6 months postinjection, femtogram levels of plasmid were detected only in muscle. Immunohistochemical analyses did not detect encoded protein in the tissues harboring residual plasmid at 1 or 7 days postinjection.

Original languageEnglish (US)
Pages (from-to)553-564
Number of pages12
JournalHuman Gene Therapy
Volume6
Issue number5
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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