Folate-Targeted Gene Transfer in Vivo

• Published in: Molecular therapy Vol. 5; no. 6; pp. 739 - 744
• Main Authors: Hofland, Hans E.J., Masson, Christophe, Iginla, Shaff, Osetinsky, Irina, Reddy, Joseph A., Leamon, Christopher P., Scherman, Daniel, Bessodes, Michel, Wils, Pierre
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2002; Elsevier Limited
• Subjects: Acids; Animals; Biodistribution; cationic liposome; folate receptor; Folic Acid - metabolism; Gene expression; Gene Targeting; Gene therapy; gene transfer; Gene Transfer Techniques; Genetic Vectors; In Vitro Techniques; Ligands; lipoplex; Liposomes - metabolism; Lung - metabolism; Lungs; Mice; Neoplasms - therapy; plasmid DNA; Polyethylene glycol; Polyethylene Glycols - metabolism; systemic; tumor targeting; Tumors; Vitamin B; United States > US; systemic; tumor targeting; plasmid DNA; gene transfer; lipoplex; folate receptor; cationic liposome
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1006/mthe.2002.0604

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.