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The present and future of nonviral delivery-based genome editing for hereditary hearing loss.

Seung Hyun Jang·Heon Yung Gee·Jinsei Jung
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Abstract

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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HumansGene EditingNanoparticlesHearing LossGenetic TherapyLipidsGene Transfer TechniquesAnimalsgene editinghearing losslipid nanoparticlesvirus-like particlesJournal ArticleReview

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Seung Hyun Jang, Heon Yung Gee, Jinsei Jung. 2026-08-05. The present and future of nonviral delivery-based genome editing for hereditary hearing loss.. https://doi.org/10.1097/moo.0000000000001151

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