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Published on: March 16, 2015
The present and future of nonviral delivery-based genome editing for hereditary hearing loss
Seung Hyun Jang1,2, Heon Yung Gee2,3, Jinsei Jung1,2,4
1Department of Otorhinolaryngology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine.
Purpose Of Review:
This review summarizes nonviral genome-editing delivery platforms for hereditary hearing loss, focusing on lipid nanoparticles (LNPs) and engineered virus-like particles (eVLPs), and discusses their advantages over adeno-associated virus-based delivery, as well as the barriers to clinical translation.
Recent Findings:
Recent advances have established LNPs as a clinically advanced nonviral platform, although challenges related to inner ear biodistribution, cell type specificity, endosomal escape, and immunogenicity remain to be addressed. In parallel, eVLPs have undergone substantial technical evolution, progressing from early low efficiency systems to advanced base editor- and prime editor-eVLP architectures that enhance cargo loading and editing efficiency. Extracellular vesicle-based genome editing has also emerged as an additional platform, although issues related to reproducibility, loading efficiency, and scalability remain major hurdles.
Summary:
Nonviral genome editing platforms expand the therapeutic toolkit for hereditary hearing loss by enabling transient delivery of genome editors with potential safety advantages. Future efforts should focus on characterizing biodistribution and immunogenicity, refining cell type-specific tropism, and establishing scalable manufacturing processes to enable successful clinical translation.
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