The project/study described was supported by Grant no.T37 MD001425-08, from the National Center of Minority Health and Health Disparities, National Institutes of Health. Its contents, including the design and conduct of the study, the collection, management, analysis and interpretation of the data, and the preparation, review, and approval of the paper, are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. No author has a financial conflict of interest in this research or in its publication. In Vitro Gene Delivery Mediated by Asialofetuin-Appended Cationic Liposomes Associated with γ-Cyclodextrin into Hepatocytes The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes) associating cyclodextrins (CyD/AF-liposomes) as a hepatocyte-selective nonviral vector. Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA) and γ-cyclodextrin (γ-CyD) (pDNA/γ-CyD/AF-liposomes) showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity. In addition, γ-CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased. γ-CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes. The stabilizing effect of γ-CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/γ-CyD/AF-liposomes. Therefore, these results suggest the potential use of γ-CyD for an enhancer of transfection efficiency of AF-liposomes. The principle of somatic gene therapy is that genes can be introduced into selected cells in the body in order to treat genetic or acquired diseases. The liver may be potentially an important target for gene therapy, because crucial diseases such as amyloidosis, primary biliary cirrhosis, familial hypercholesteremia, phenyl ketonuria, and virus hepatitis occur in this organ [1] . In addition, the liver has the ability to synthesize a wide variety of proteins, to perform various posttranslational modifications, and to secrete them into the blood.