Helper-dependent adenoviral vector-mediated long-term expression of human apolipoprotein A-I reduces atherosclerosis in apo E-deficient mice》.pdfVIP

Gene 327 (2004) 153–160 /locate/gene Helper-dependent adenoviral vector-mediated long-term expression of human apolipoprotein A-I reduces atherosclerosis in apo E-deficient mice a,b,*, L. Maria Belalcazarc,1 c a a Lucio Pastore , Kazuhiro Oka , Racel Cela , Brendan Lee , Lawrence Chanc, Arthur L. Beaudetc a Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA b CEINGE-Biotecnologie Avanzate, Via Comunale Margherita 482, 80145, Naples, Italy c Departments of Molecular and Cell Biology and Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA Received 25 July 2003; received in revised form 30 September 2003; accepted 14 November 2003 Received by F. Salvatore Abstract Apolipoprotein A-I (APOA-I) is the major protein component of high-density lipoproteins (HDL). It has been shown that over-expression of human APOA-I increases HDL cholesterol and decreases atherosclerosis. We constructed a helper-dependent adenoviral (HD-Ad) vector 13 that contains the entire human APOA-I gene (hgAI). Intravenous delivery of 1 10 viral particles/kg of this vector was followed by high levels of human APOA-I expression (up to 200 mg/dl) in the absence of detectable hepatic toxicity. We treated apo E-defic