Effective restoration of dystrophin‐associated proteins in vivo by adenovirus‐mediated transfer of truncated dystrophin cDNAs

FEBS Letters

Nabeshima, Yo-ichi²  Dickson, George¹  Yuasa, Katsutoshi²  Takeda, Shin'ichi²  Miyagoe, Yuko²  Yamamoto, Kanji² 

[1] School of Biological Sciences, Royal Holloway College, University of London, Surrey TW20 0EX, UK;Department of Molecular Genetics, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187, Japan

关键词: Dystrophin;    Duchenne muscular dystrophy;    Gene therapy;    Adenovirus vector;    Rod domain;    Ad;    adenovirus;    AAV;    adeno-associated virus;    BMD;    Becker muscular dystrophy;    DAP;    dystrophin-associated protein;    DMD;    Duchenne muscular dystrophy;    DMEM;    Dulbecco's modified Eagle's medium;    moi;    multiplicity of infection;    pfu;    plaque-forming units;    PBS;    phosphate-buffered saline;    TA;    tibialis anterior;    PCR;    polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(98)00251-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A series of truncated dystrophin cDNAs (3.1–4.2 kbp) containing only three, three, two or one rod repeats with hinge 1 and 4 (named ΔDysAX2, AX11, AH3, M3, respectively) or no rod repeat retaining either hinge 1 or 4 (named ΔDysH1, H4, respectively) were constructed. These cDNAs were introduced into skeletal muscle of adult mdx mice using the adenovirus vector with a strong CAG promoter. ΔDysAX2, AX11, AH3 and ΔDysM3 expressed themselves successfully and recovered dystrophin-associated proteins effectively. Especially 3.7 kbp cDNA for ΔDysM3 offers the possibility of an approach utilizing newly developed virus vectors, such as an adeno-associated virus vector, toward gene therapy of Duchenne muscular dystrophy.

【 授权许可】

Unknown