Multiple systemic expression of human interferon-beta in mice can be achieved upon repeated administration of optimized pcTG90-lipoplex.

Abstract:

:The possibility of achieving multiple systemic expression of human interferon-beta in mice upon repeated intravenous administration of cationic liposome-DNA complex (lipoplex) was investigated. Lipoplexes containing the pentammonio lipid pcTG90 were first optimized by selecting the most efficient ratio of pcTG90 to phosphatidylethanolamine (DOPE) and the N/P ratio of cationic lipid nitrogen to DNA phosphate. Highest levels and reproducibility of gene expression were obtained using pcTG90/DOPE (1:2) liposomes complexed with the IFNB1 gene containing plasmid pTG14169 at a N/P ratio of 10. Following lipoplex administration, an early but transient human interferon-beta expression in serum was observed. Importantly, repeated systemic gene expression could be achieved upon re-administration with a minimal time interval of 14 days between two injections. For an interval period of 6 days, subsequent gene expression was inhibited by a first administration of lipoplexes containing either a luciferase reporter gene plasmid or an empty plasmid, but was not inhibited when free (non-complexed) plasmid pTG14169 was first injected. Multiple injections of pcTG90-lipoplex performed once every other month resulted in three subsequent peaks of systemic IFNB1 gene expression in mice. In conclusion, our study demonstrates the feasibility of expanding the therapeutic window of a cytokine using repetitive intravenous administration of lipoplex.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Meyer O,Schughart K,Pavirani A,Kolbe HV

doi

10.1038/sj.gt.3301289

keywords:

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

1606-11

issue

18

eissn

0969-7128

issn

1476-5462

journal_volume

7

pub_type

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