Retroviral‐mediated transfer of a dystrophin minigene into <i>mdx</i> mouse myoblasts in vitro

Dunckley, Matthew G.; Love, Donald R.; Davies, Kay E.; Walsh, Frank S.; Morris, Glenn E.; Dickson, George

doi:10.1016/0014-5793(92)80363-l

Cited by 76 publications

(28 citation statements)

References 33 publications

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“…In fact, the poor level of transduction in mature muscle with various viral vectors (adenovirus, retrovirus and herpes simplex virus) remains a major obstacle to the application of gene therapy for DMD. [36][37][38][39][40][41][42][52][53][54] To compare the relative dystrophin gene transfer efficiency between dystrophin-containing adenoviral particles for direct injection with that obtained when the same adenovirus preparation is used in an ex vivo protocol, 1 × 10 7 AdDYS␤gal viral particles were either injected directly into an mdx leg muscle site, or used to infect 1 × 10 6 primary mdx muscle cells that were subsequently injected into the contralateral mdx leg muscle site. Analysis of the sites 5 days after injection indicated a nearly 10-fold greater number of dystrophin-positive muscle fibers in mdx sites treated with the ex vivo cell transfer protocol compared with that obtained via direct adenovirus injection (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35] Retroviral vectors are capable of introducing truncated dystrophin to dystrophic myoblasts in vitro, but are unable to efficiently transduce differentiated muscle cells such as myotubes and myofibers, since they require dividing cells for integration and expression. 36,37 While adenovirus (AV) appears to be a relatively good vector for skeletal muscle cells, there are potential limitations to the use of AV as a gene delivery vector to muscle, ie the differential transducibility of myofibers throughout muscle maturation; the immune rejection induced by first generation adenoviral vectors; and the high titer of viral recombinants that is often required for successful muscle transduction. [38][39][40][41][42][43][44][45][46][47] Recent studies with mutant AV vectors in which all viral genes were removed, suggest that these vectors may be able to circumvent the immunological problems due to viral antigens.…”

Section: Introductionmentioning

confidence: 99%

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Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles

et al. 1998

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Duchenne muscular dystrophy (DMD) is an X-linked associated proteins. A greater amount of dystrophin recessive muscle disease characterized by a lack of dysreplacement occurred in mdx muscle following transplantrophin expression. Myoblast transplantation and gene tation of mdx myoblasts isolated from a transgenic mouse therapy have the potential of restoring dystrophin, thus overexpressing dystrophin suggesting that engineering decreasing the muscle weakness associated with this disautologous myoblasts to express high amounts of dystroease. In this study we present data on the myoblast phin might be beneficial. The ex vivo approach possesses mediated ex vivo gene transfer of full-length dystrophin to attributes that make it useful for gene transfer to skeletal mdx (dystrophin deficient) mouse muscle as a model for muscle including: (1) creating a reservoir of myoblasts capautologous myoblast transfer. Both isogenic primary mdx able of regenerating and restoring dystrophin to dystrophic myoblasts and an immortalized mdx cell line were transmuscle; and (2) achieving a higher level of gene transfer duced with an adenoviral vector that has all viral coding to dystrophic muscle compared with adenovirus-mediated sequences deleted and encodes ␤-galactosidase and fulldirect gene delivery. However, as observed in direct gene length dystrophin. Subsequently, these transduced myotransfer studies, the ex vivo approach also triggers a cellublasts were injected into dystrophic mdx muscle, where the lar immune response which limits the duration of transinjected cells restored dystrophin, as well as dystrophingene expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles

et al. 1998

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“…Researchers have demonstrated that a truncated (6.3 kb) human dystrophin cDNA can be retrovirally transduced and expressed in mdx mouse myoblasts in vitro (Dunckley et al, 1992), and that retroviral transduction of activated satellite cells in regenerating skeletal muscle can facilitate direct and stable dystrophin gene transfer into muscle tissues in vivo (Dunckley et al, 1993). Because the retrovirus requires dividing cells for its integration, the ongoing process of muscle degeneration and regeneration that occurs in mdx mouse skeletal muscle is thought to promote the efficient retroviral transduction observed in skeletal muscle in vivo.…”

Section: Introduction D Uchenne's Muscular Dystrophy (Dmd) Is Charactmentioning

confidence: 99%

Dystrophin Delivery in Dystrophin-Deficient DMD^mdxSkeletal Muscle by Isogenic Muscle-Derived Stem Cell Transplantation

Ikezawa

Cao

et al. 2003

Human Gene Therapy

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Duchenne's muscular dystrophy (DMD) is a lethal muscle disease caused by a lack of dystrophin expression at the sarcolemma of muscle fibers. We investigated retroviral vector delivery of dystrophin in dystrophin-deficient DMD(mdx) (hereafter referred to as mdx) mice via an ex vivo approach using mdx muscle-derived stem cells (MDSCs). We generated a retrovirus carrying a functional human mini-dystrophin (RetroDys3999) and used it to stably transduce mdx MDSCs obtained by the preplate technique (MD3999). These MD3999 cells expressed dystrophin and continued to express stem cell markers, including CD34 and Sca-1. MD3999 cells injected into mdx mouse skeletal muscle were able to deliver dystrophin. Though a relatively low number of dystrophin-positive myofibers was generated within the gastrocnemius muscle, these fibers persisted for up to 24 weeks postinjection. The injection of cells from additional MDSC/Dys3999 clones into mdx skeletal muscle resulted in varying numbers of dystrophin-positive myofibers, suggesting a differential regenerating capacity among the clones. At 2 and 4 weeks postinjection, the infiltration of CD4- and CD8-positive lymphocytes and a variety of cytokines was detected within the injected site. These data suggest that the transplantation of retrovirally transduced mdx MDSCs can enable persistent dystrophin restoration in mdx skeletal muscle; however, the differential regenerating capacity observed among the MDSC/Dys3999 clones and the postinjection immune response are potential challenges facing this technology.

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“…Effective gene therapy for DMD will require the transfer of adequate copies of either the full-length dystrophin gene or dystrophin minigenes in affected muscle to restore adequate production of dystrophin for compensation of the weakness. [6][7][8][9][10] The transplantation of normal myoblasts into dystrophin-deficient muscle to create a reservoir of dystrophinproducing myoblasts capable of fusing with dystrophic myofibers has been studied extensively in both mdx mice (an animal model for DMD) and DMD patients. [11][12][13][14][15][16] Although these studies showed transient restoration of dystrophin and increase of strength in dystrophic muscle, the limited success of myoblast transplantation has been related to immune rejection, poor survival and limited spread of injected myoblasts after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Matching host muscle and donor myoblasts for myosin heavy chain improves myoblast transfer therapy

Huard

2000

Gene Ther

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Intensive efforts have been made to develop an effective therapy for Duchenne muscular dystrophy (DMD). Although myoblast transplantation has been found capable of transiently delivering dystrophin and improving the strength of the injected dystrophic muscle, this approach has been hindered by the immune rejection problems as well as the poor survival and limited spread of the injected cells. In the present study, we have investigated whether the careful selection of donor myoblasts and host muscle for the myosin heavy chain expression (MyHCs) plays a role in the success of myoblast transfer. Highly purified normal myoblasts derived from the m. soleus and m. gastrocnemius white of normal mice were transplanted into the m. soleus (containing 70% of type I fibers) and gastrocnemius white (100% of type II

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Retroviral‐mediated transfer of a dystrophin minigene into mdx mouse myoblasts in vitro

Cited by 76 publications

References 33 publications

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles

Dystrophin Delivery in Dystrophin-Deficient DMD^mdxSkeletal Muscle by Isogenic Muscle-Derived Stem Cell Transplantation

Matching host muscle and donor myoblasts for myosin heavy chain improves myoblast transfer therapy

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Retroviral‐mediated transfer of a dystrophin minigene into mdx mouse myoblasts in vitro

Cited by 76 publications

References 33 publications

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles

Dystrophin Delivery in Dystrophin-Deficient DMDmdxSkeletal Muscle by Isogenic Muscle-Derived Stem Cell Transplantation

Matching host muscle and donor myoblasts for myosin heavy chain improves myoblast transfer therapy

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Dystrophin Delivery in Dystrophin-Deficient DMD^mdxSkeletal Muscle by Isogenic Muscle-Derived Stem Cell Transplantation