Targeted gene delivery to pulmonary endothelium by anti-PECAM antibody

To achieve efficient systemic gene delivery to the lung with minimal toxici ty, a vector was developed by chemically conjugating a cationic polymer, po lyethylenimine (PEI), with anti-platelet endothelial cell adhesion molecule (PECAM) antibody (Ab). Transfection of mouse lung endothelial cells with a plasmid expression vector with cDNA to luciferase (pCMVL) complexed with a nti-PECAM Ab-PEI conjugate was more efficient than that with PEI-pCMVL comp lexes. Furthermore, the anti-PECAM Ab-PEI conjugate mediated efficient tran sfection at lower charge plus-to-minus ratios. Conjugation of PEI with a co ntrol IgG (hamster IgG) did not enhance transfection of mouse lung endothel ial cells, suggesting that the cellular uptake of anti-PECAM Ab-PEI-DNA com plexes and subsequent gene expression were governed by a receptor-mediated process rather than by a nonspecific charge interaction. Conjugation of PEI with anti-PECAM Ab also led to significant improvement in lung gene transf er to intact mice after intravenous administration. The increase in lung tr ansfection was associated with a decrease compared with PEI-pCMVL with resp ect to circulating proinflammatory cytokine (tumor necrosis factor-alpha) l evels. These results indicate that targeted gene delivery to the lung endot helium is an effective strategy to enhance gene delivery to the pulmonary c irculation while simultaneously reducing toxicity.