Transfection of Folate-Polylysine DNA Complexes: Evidence for Lysosomal Delivery

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Abstract
We are utilizing the folate receptor for the intracellular delivery of DNA. In this study, a folate-poly-L-lysine (FPLL) conjugate was synthesized and equilibrated with plasmid DNA encoding the firefly luciferase gene. The FPLL-DNA complexes were added to KB cells treated with chloroquine. Luciferase activity of cells incubated with FPLL-DNA was 6-fold higher than of cells exposed to poly-L-lysine (PLL)-DNA. The addition of free folic acid competitively inhibited the enhancement of gene expression. Removal of chloroquine from the media significantly inhibited transfection efficiency of FPLL-DNA complexes. We conclude that FPLL-DNA complexes are delivered into KB cells via folate receptor-mediated endocytosis and likely follow a lysosomal pathway into the cytoplasm.

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