Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression.
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.
Gottschalk
S
S
Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Cristiano
R J
RJ
Smith
L C
LC
Woo
S L
SL
D000256:Adenoviridae / Q000235:genetics; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000235:genetics; D016503:Drug Delivery Systems; D004705:Endocytosis; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004274:DNA, Recombinant; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine; D005492:Folic Acid