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Titolo:
Analysis of muscle creatine kinase regulatory elements in recombinant adenoviral vectors
Autore:
Hauser, MA; Robinson, A; Hartigan-OConnor, D; Williams-Gregory, D; Buskin, JN; Apone, S; Kirk, CJ; Hardy, S; Hauschka, SD; Chamberlain, JS;
Indirizzi:
Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Human Genet, Ann Arbor, MI 48109 USA Univ Michigan, Ctr Gene Therapy, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 ene Therapy, Ann Arbor, MI 48109 USA Univ Michigan, Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 & Mol Biol, Ann Arbor, MI 48109 USA Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA Univ Michigan Ann ArborMI USA 48109 , Dept Surg, Ann Arbor, MI 48109 USA Univ Washington, Dept Biochem, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 Dept Biochem, Seattle, WA 98195 USA Chiron Corp, Emeryville, CA 94608 USA Chiron Corp Emeryville CA USA 94608Chiron Corp, Emeryville, CA 94608 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 1, volume: 2, anno: 2000,
pagine: 16 - 25
SICI:
1525-0016(200007)2:1<16:AOMCKR>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
TISSUE-SPECIFIC EXPRESSION; MEDIATED GENE-TRANSFER; TRANSGENIC MDX MICE; CARDIAC-MUSCLE; IN-VIVO; SKELETAL-MUSCLE; MOUSE MYOBLASTS; DENDRITIC CELLS; FULL-LENGTH; ENHANCER;
Keywords:
adenovirus; muscle-specific; muscle creatine kinase; dendritic cell; muscular dystrophy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Chamberlain, JS Univ Michigan, Sch Med, Dept Human Genet, 1150 W Med Ctr DR, Ann Arbor, MI48109 USA Univ Michigan 1150 W Med Ctr DR Ann Arbor MI USA 48109 USA
Citazione:
M.A. Hauser et al., "Analysis of muscle creatine kinase regulatory elements in recombinant adenoviral vectors", MOL THER, 2(1), 2000, pp. 16-25

Abstract

Adenoviral gene transfer holds promise for gene therapy, but effective transduction of id large and distributed tissue such as muscle will almost certainly require systemic delivery. In this context, the use of muscle-specific regulatory elements such as the muscle creatine kinase (MCK) promoter and enhancer will avoid potentially harmful ectopic expression of transgenes. We describe here the development and testing of adenoviral vectors containing small, striated muscle-specific, highly active MCK expression cassettes. One of these regulatory elements (CK6) is less than 600 bp in length and is 12% as active as the CMV promoter/enhancer in muscle. A recombinant adenoviral vector containing this regulatory element retains very high muscle specificity, expressing 600-fold higher levels of transgene in muscle than in liver. Muscle-specific regulatory elements may also increase persistence of transduced muscle cells. Adenoviral transduction of dendritic cells has been shown to stimulate cytotoxic T-lymphocyte (CTL) responses directed against transgene epitopes. We show that human dendritic cells infected in vitro with MCK-containing adenoviruses do not express significant levels of transgene. Furthermore, while adenoviral vectors containing nonspecific promoters are normally cleared from muscle tissue within 1 month, we show that MCK-containing vectors express significant levels of transgene 4 months after intramuscular injection.

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Documento generato il 26/09/20 alle ore 14:49:26