Nucleic Acids Research, Vol 24, Issue 11 2176-2182, Copyright © 1996 by Oxford University Press
A Bielinska, JF Kukowska-Latallo, J Johnson, DA Tomalia and JR Baker Jr
Starburst polyamidoamine (PAMAM) dendrimers are a new type of synthetic
polymer characterized by a branched spherical shape and a high density
surface charge. We have investigated the ability of these dendrimers to
function as an effective delivery system for antisense oligonucleotides and
'antisense expression plasmids' for the targeted modulation of gene
expression. Dendrimers bind to various forms of nucleic acids on the basis
of electrostatic interactions, and the ability of DNA-dendrimer complexes
to transfer oligonucleotides and plasmid DNA to mediate antisense
inhibition was assessed in an in vitro cell culture system. Cell lines that
permanently express luciferase gene were developed using dendrimer mediated
transfection. Transfections of antisense oligonucleotides or antisense cDNA
plasmids into these cell lines using dendrimers resulted in a specific and
dose dependent inhibition of luciferase expression. This inhibition caused
approximately 25-50% reduction of baseline luciferase activity. Binding of
the phosphodiester oligonucleotides to dendrimers also extended their
intracellular survival. While dendrimers were not cytotoxic at the
concentrations effective for DNA transfer, some non-specific suppression of
luciferase expression was observed. Our results indicate that Starburst
dendrimers can be effective carriers for the introduction of regulatory
nucleic acids and facilitate the suppression of the specific gene
expression.
ARTICLES
Regulation of in vitro gene expression using antisense oligonucleotides or antisense expression plasmids transfected using starburst PAMAM dendrimers
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0666, USA.
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