The BV2 peptide significantly enhanced delivery of phosphorodiamidate morpholino oligomer to cardiac and skeletal muscles, restoring dystrophin levels in dystrophin-deficient mice.
Does BV2 peptide-mediated delivery improve the targeting and efficacy of biotherapeutics in skeletal and cardiac muscles in mouse models of muscular dystrophy and atrophy?
The BV2 peptide effectively targets biotherapeutics to skeletal and cardiac muscle, offering a promising delivery platform for treating muscular and cardiac disorders like Duchenne Muscular Dystrophy.
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Although peptide-based delivery strategies show promise for muscle and heart diseases, delivery of biotherapeutics to both skeletal and cardiac muscles remains challenging. Here, we identified a muscle-homing peptide (BV2) against blood vessel epicardial substance (BVES) by phage display. BV2 shows high binding affinity to BVES and is internalized primarily via caveolae-mediated endocytosis. Importantly, BV2 enables efficient delivery of Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomer (PMO), mCherry protein and exosomes to skeletal muscle and heart in vivo. BV2-mCherry protein and BV2-E31R anti-myostatin peptide were effectively delivered to muscle layers when microneedles loaded with these biotherapeutics were implanted on hindlimbs of mice. Muscle mass and myofiber size also significantly increased in muscle atrophy mice grafted with BV2-E31R microneedles. Moreover, significantly enhanced restoration of dystrophin protein was achieved in peripheral and cardiac muscles of dystrophin-deficient mdx and dystrophin/utrophin double-knockout mice when exosomes simultaneously modified with BV2 and PMO. These findings highlight the potency of BV2 in directing targeted delivery of diverse biotherapeutics to muscle and heart, thus providing an effective tool for DMD and other muscular and cardiac disorders.
Wang et al. (Sun,) reported a other. The BV2 peptide significantly enhanced delivery of phosphorodiamidate morpholino oligomer to cardiac and skeletal muscles, restoring dystrophin levels in dystrophin-deficient mice.