Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression.

Abstract:

:We have used a particular folate receptor, which is overexpressed in tumor cells, for targeted DNA delivery into these cell types. This folate receptor internalizes folate through caveolae by a process named potocytosis, which is distinct from endocytosis, through clathrin-coated pits. When folate conjugated to poly-L-lysine was used to deliver the E. coli beta-galactosidase gene into tumor cells overexpressing the folate receptor, only low levels of beta-galactosidase activity were detectable. When a replication-defective adenovirus was coincubated with the DNA/folate complexes, 20 to 30% of the cells stained blue with X-gal and a 1000-fold increase of beta-galactosidase activity was observed. Thus, for high efficient DNA delivery and gene expression via the caveolae system, a potosomal disruption agent is needed. Furthermore, folate-mediated DNA delivery is restricted to tumor cells that highly overexpress the folate receptor, which will permit future development of tumor cell-specific delivery of toxic genes for cancer gene therapy.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Gottschalk S,Cristiano RJ,Smith LC,Woo SL

subject

Has Abstract

pub_date

1994-05-01 00:00:00

pages

185-91

issue

3

eissn

0969-7128

issn

1476-5462

journal_volume

1

pub_type

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