Folate-targeted gene transfer in vivo.
Nonviral systemic delivery is one of the most attractive approaches for cancer gene therapy. To achieve this goal, various laboratories have developed cationic liposomes. However, when injected intravenously, cationic lipid-DNA complexes accumulate mostly into and transfect lung tissue. Here, we describe a method by which these complexes can be targeted to tumors using folic acid. Adding polyethylene glycol (PEG)-lipids to the complexes dramatically reduced both lung accumulation and gene transfer to lungs and tumors after intravenous administration. The presence of folic acid at the distal end of the PEG-lipid did not modify tumor accumulation of the complexes. However, with folate-targeted complexes, gene transfer activity was restored in tumors while the activity in lungs was reduced by 50- to 100-fold compared with nontargeted lipid-DNA complexes. This approach provides a first in vivo proof of concept to achieve targeted tumor gene delivery.
Hofland
Hans E J
HE
Gencell, Aventis Pharma, 3825 Bay Center Place, Hayward, California 94545, USA.
Masson
Christophe
C
Iginla
Shaff
S
Osetinsky
Irina
I
Reddy
Joseph A
JA
Leamon
Christopher P
CP
Scherman
Daniel
D
Bessodes
Michel
M
Wils
Pierre
P
D000818:Animals; D005492:Folic Acid / Q000378:metabolism*; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D066298:In Vitro Techniques; D008081:Liposomes / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D011092:Polyethylene Glycols / Q000378:metabolism
D008081:Liposomes; D011092:Polyethylene Glycols; D005492:Folic Acid