Non-viral gene therapy for neuromuscular diseases including Duchenne muscular dystrophy using nanovesicles derived from human cells

One of the biggest challenges in AAV gene delivery for Duchenne muscular dystrophy (DMD) is that some patients cannot be treated due to pre-existing neutralizing antibodies. As an alternative, nanovesicles derived from diverse human cells have emerged as highly efficient delivery vehicles for genetic materials. This is due to their superior biocompatibility and capability to cross diverse tissue barriers. Notably, the lack of strong host immune response was witnessed in multiple preclinical studies, as well as clinical trials recently completed using human allogeneic nanovesicles. Engineering nanovesicles with tissue-specific ligands on the surface can also enhance tissue selectivity, thus reducing off-target effects. Taken together, these findings raise the possibility that this novel non-viral approach can serve as an attractive alternative to risk-prone viral-mediated gene therapy. This review discusses the recent advances in a non-viral gene therapy approach using cell-derived nanovesicles, and highlights their therapeutic potential in treating neuromuscular diseases, such as DMD, along with current challenges that need to be further addressed.