title: Comparison of efficacy of the disease-specific LOX1- and constitutive cytomegalovirus-promoters in expressing interleukin 10 through adeno-associated virus 2/8 delivery in atherosclerotic mice.
abstract: The development of gene therapy vectors for treating diseases of the cardiovascular system continues at a steady pace. Moreover, in the field of gene therapy the utility of "disease-specific promoters" has strong appeal. Many therapeutic genes, including transforming growth factor beta 1 or interleukin 10, are associated to adverse effects. The use of a disease-specific promoter might minimize toxicity. The lectin-like oxidized low density lipoprotein receptor 1 is a marker of cardiovascular disease and a potential therapeutic target. The lectin-like oxidized low density lipoprotein receptor 1 is known to be up-regulated early during disease onset in a number of cell types at the sites where the disease will be clinically evident. In this study an adeno-associated virus-2 DNA vector (AAV2) using the AAV8 capsid, and containing the full length The lectin-like oxidized low density lipoprotein receptor 1 promoter, was generated and assayed for its ability to express human interleukin 10 in low density lipoprotein receptor knockout mice on high cholesterol diet. The cytomegalovirus early promoter was used for comparison in a similarly structured vector. The two promoters were found to have equal efficacy in reducing atherogenesis as measured by aortic systolic blood velocity, aortic cross sectional area, and aortic wall thickness. This is the first head-to-head comparison of a constitutive with a disease-specific promoter in a therapeutic context. These data strongly suggest that the use of a disease-specific promoter is appropriate for therapeutic gene delivery.
authors.affiliation: Medical Research Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Hongqing
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Medical Research Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Maohua
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Internal Medicine, Division of Hematology & Oncology, Texas Tech University, Health Sciences Center, School of Medicine, Lubbock, Texas, United States of America.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mirandola
authors.affiliation: Department of Internal Medicine, Division of Hematology & Oncology, Texas Tech University, Health Sciences Center, School of Medicine, Lubbock, Texas, United States of America; Kiromic LLC, Lubbock, Texas, United States of America.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Figueroa
authors.affiliation: Department of Internal Medicine, Division of Hematology & Oncology, Texas Tech University, Health Sciences Center, School of Medicine, Lubbock, Texas, United States of America; Kiromic LLC, Lubbock, Texas, United States of America.
authors.forename: Everardo
authors.initials: E
authors.lastname: Cobos
authors.affiliation: Department of Internal Medicine, Division of Hematology & Oncology, Texas Tech University, Health Sciences Center, School of Medicine, Lubbock, Texas, United States of America; Kiromic LLC, Lubbock, Texas, United States of America.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
authors.affiliation: Medical Research Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hermonat
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D001783:Blood Flow Velocity / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051127:Scavenger Receptors, Class E / Q000235:genetics*; D019076:Transgenes / Q000235:genetics
chemical_list: C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D016753:Interleukin-10
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