Entry of enveloped viruses into cells is mediated by viral fusogenic proteins that drive membrane rearrangements needed for fusion between viral and target membranes. Skeletal muscle development also requires membrane fusion events between progenitor cells to form multinucleated myofibers. Myomaker and Myomerger are muscle-specific cell fusogens but do not structurally or functionally resemble classical viral fusogens. We asked whether the muscle fusogens could functionally substitute for viral fusogens, despite their structural distinctiveness, and fuse viruses to cells. We report that engineering of Myomaker and Myomerger on the membrane of enveloped viruses leads to specific transduction of skeletal muscle. We also demonstrate that locally and systemically injected virions pseudotyped with the muscle fusogens can deliver μDystrophin to skeletal muscle of a mouse model of Duchenne muscular dystrophy and alleviate pathology. Through harnessing the intrinsic properties of myogenic membranes, we establish a platform for delivery of therapeutic material to skeletal muscle.

有包膜病毒进入细胞是由病毒融合蛋白介导的，该蛋白驱动病毒和目标膜之间融合所需的膜重排。骨骼肌发育还需要祖细胞之间的膜融合事件以形成多核肌纤维。Myomaker 和 Myomerger 是肌肉特异性细胞融合剂，但在结构或功能上与经典病毒融合剂不同。我们询问肌肉融合剂是否可以在功能上替代病毒融合剂，并将病毒融合到细胞中，尽管它们的结构独特。我们报告说，Myomaker 和 Myomerger 在包膜病毒膜上的工程导致了骨骼肌的特异性转导。我们还证明，局部和全身注射用肌肉融合剂假型化的病毒粒子可以将μ肌营养不良蛋白递送至杜氏肌营养不良症小鼠模型的骨骼肌并缓解病理。通过利用生肌膜的内在特性，我们建立了一个将治疗材料输送到骨骼肌的平台。