Effective repetitive dystrophin gene transfer into skeletal muscle of adult <i>mdx</i> mice using a helper‐dependent adenovirus vector expressing the coxsackievirus and adenovirus receptor (CAR) and dystrophin

Uchida, Yuji; Maeda, Yasushi; Kimura, En; Nishida, Yoshiaki; Arima, Toshiyuki; Hirano, Teruyuki; Uyama, Eiichiro; Mita, Shuji; Uchino, Makoto

doi:10.1002/jgm.745

Cited by 9 publications

(1 citation statement)

References 35 publications

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“…DMD muscles lack the dystrophin protein, and dystrophin gene replacement is expected to halt ongoing myofiber turnover. To drive the transcription of various genes in gene therapy protocols, several strong viral enhancer/promoters were used in previous studies, including cytomegalovirus (CMV) [11], [12],[13], Raus sarcoma virus (RSV) [14], [15], [16], cytomegalovirus enhancer, chicken beta-actin (CAG) promoter [16], [17], [18], [19], murine stem cell virus (MSCV) [16], [17], [20], [21], mouse phosphoglycerate-kinase 1 (pGK) [12], [22], [23], and elongation factor 1 (EF1) [12], [24], which are ubiquitous promoters derived from house keeping gene regulation systems in mammalian cells. As the MSCV promoter drives gene expression as strongly as the CMV promoter and achieves stable gene expression in different type of cells, especially muscle fibers, we previously used the MSCV promoter to regulate the expression of a short version of the dystrophin gene in a lentiviral vector [6].…”

Section: Introductionmentioning

confidence: 99%

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

et al. 2011

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Variations in gene promoter/enhancer activity in different muscle fiber types after gene transduction was noticed previously, but poorly analyzed. The murine stem cell virus (MSCV) promoter drives strong, stable gene expression in hematopoietic stem cells and several other cells, including cerebellar Purkinje cells, but it has not been studied in muscle. We injected a lentiviral vector carrying an MSCV-EGFP cassette (LvMSCV-EGFP) into tibialis anterior muscles and observed strong EGFP expression in muscle fibers, primary cultured myoblasts, and myotubes isolated from injected muscles. We also generated lentiviral-mediated transgenic mice carrying the MSCV-EGFP cassette and detected transgene expression in striated muscles. LvMSCV-EGFP transgenic mice showed fiber type-dependent variations in expression: highest in types I and IIA, intermediate in type IID/X, and lowest in type IIB fibers. The soleus and diaphragm muscles, consisting mainly of types I and IIA, are most severely affected in the mdx mouse model of muscular dystrophy. Further analysis of this promoter may have the potential to achieve certain gene expression in severely affected muscles of mdx mice. The Lv-mediated transgenic mouse may prove a useful tool for assessing the enhancer/promoter activities of a variety of different regulatory cassettes.

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Section: Introductionmentioning

confidence: 99%

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

et al. 2011

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Gene Therapy for Duchenne Muscular Dystrophy

Putten

Aartsma‐Rus

2013

Encyclopedia of Life Sciences

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Duchenne muscular dystrophy is a severe muscle wasting disorder caused by lack of functional dystrophin, due to reading‐frame disrupting mutations in the DMD gene. There is no cure, but several genetic therapeutic approaches aiming to delay disease progression by restoring, manipulating or replacing the DMD gene are under investigation in (pre)clinical settings. The antisense‐mediated exon skipping approach, which restores the disrupted reading frame allowing synthesis of partly functional dystrophin proteins is closest to clinical application. The first trials with viral vectors to deliver minidystrophin genes and compounds to force readthrough of premature stop codons by the translation machinery have also been undertaken, whereas other approaches, like genome editing, are still in the early development phase. Despite some remaining hurdles that have to be overcome, lessons learned can be used to catalyse the development of potential therapies. Key Concepts: Duchenne muscular dystrophy (DMD) is caused by reading‐frame disrupting mutations in the DMD gene, resulting in premature termination of dystrophin synthesis. Inframe mutations allow synthesis of shorter, but partly functional dystrophin proteins, resulting in the milder Becker muscular dystrophy (BMD) phenotype. Antisense oligonucleotide‐mediated exon skipping aims to restore the reading frame enabling synthesis of BMD‐like dystrophins, thereby converting the severe DMD into the milder BMD disease. Gene replacement therapy (replacing the dysfunctional dystrophin cDNA) is hampered by the size and complexity of the DMD gene and dystrophin cDNA. AAV vectors have a limited loading capacity of ∼4.5 kb, requiring the use of mini‐, or microdystrophin genes that encode only the most crucial functional domains. Ataluren can be used to force the translational machinery to ignore premature stop codons enabling synthesis of intact dystrophin. Endonuclease‐mediated generation of double‐strand breaks can be used to correct the genetic mutation or restore the reading frame. Many therapeutic approaches have progressed to clinical trials.

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A retrovirus‐based system to stably silence GDF‐8 expression and enhance myogenic differentiation in human rhabdomyosarcoma cells

Yang

Zhang

Cong

et al. 2008

The Journal of Gene Medicine

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Effective repetitive dystrophin gene transfer into skeletal muscle of adult mdx mice using a helper‐dependent adenovirus vector expressing the coxsackievirus and adenovirus receptor (CAR) and dystrophin

Cited by 9 publications

References 35 publications

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

Gene Therapy for Duchenne Muscular Dystrophy

A retrovirus‐based system to stably silence GDF‐8 expression and enhance myogenic differentiation in human rhabdomyosarcoma cells

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