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Herein, we report the first instances of extrahepatic DNA\u2010LNP targeting. DNA\u2010LNPs conjugated to antibodies against PECAM\u20101 or VCAM\u20101 target the endothelium of the lungs and brain\/spleen, respectively. These LNPs drive robust transgene expression in their target organs, with greater magnitude and duration than untargeted LNPs. Lung specificity of PECAM\u2010targeted transgene expression increases over two weeks, resulting in markedly higher lung\u2010to\u2010liver expression ratios than our previous PECAM\u2010targeted mRNA\u2010LNPs. Off\u2010target liver DNA expression declines to undetectable levels but persists in the lungs, while mRNA expression uniformly decreases due to its short half\u2010life. We further improve this expression specificity by replacing full\u2010length antibodies with Fab fragments. Single\u2010cell analysis reveals a key mechanism underlying the improvements in organ\u2010specificity: target organ expression is dominated by long\u2010lived endothelial cells, while off\u2010target liver delivery and expression are in non\u2010endothelial cells with shorter half\u2010lives. 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