Aug 2026· Science Advances· Vol 12· 0 citations· 91 references
Medicine
TL;DR
A charge-altering releasable transporter (CART) that delivers RNA selectively to the corneal endothelium, a non-regenerative cell layer whose dysfunction underlies several blinding conditions and establishes CARTs as a platform for non-viral gene delivery to the eye, with the potential to treat corneal dystrophies and other vision disorders.
Abstract
RNA therapies hold tremendous promise for treating genetic eye diseases. However, their development is limited by the lack of non-viral delivery platforms that can target specific ocular cell types. Here, we describe a charge-altering releasable transporter (CART) that delivers RNA selectively to the corneal endothelium, a non-regenerative cell layer whose dysfunction underlies several blinding conditions. We characterize the safety of CART-RNA nanoparticles in mice and show that they facilitate delivery of diverse RNA cargoes to the corneal endothelium, including circular RNA and CRISPR/Cas9. We verify that these nanoparticles can be redosed and apply them to achieve corneal gene editing. We further demonstrate CART transfection of corneal endothelial cells from a human donor in vitro and in a non-human primate in vivo, supporting the feasibility of clinical translation. Our findings establish CARTs as a platform for non-viral gene delivery to the eye, with the potential to treat corneal dystrophies and other vision disorders.
This review systematically compares traditional and emerging methods for exosome isolation and purification, and discusses their expanding roles: (1) as diagnostic biomarkers and (2) as therapeutic agents or drug delivery systems, with an emphasis on representative examples and engineering innovations.
Xuan Liao, Hongkai Gao, Mengtian Bai et al.· Frontiers in Cell and Develo...· 0 citations
Overall, exosome-based therapies hold substantial promise for transforming the management of corneal diseases, but further rigorous translational and clinical studies are required to realize their full potential.
Ningjing Tang, Xiya Yin, Andrew J W Huang et al.· MedScience· 0 citations
This review critically examines recent progress in engineering delivery systems to access representative extrahepatic tissues, including the central nervous system (CNS), eye, lung, heart, spleen, inner ear, and bone marrow, and evaluates the rational design of viral vectors, polymeric and lipid-based nanocarriers, exosome platforms, hydrogel depot systems, and local administration strategies that bypass systemic clearance.
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.
S. H. Jang, H. Gee, Jinsei Jung· Current Opinion in Otolaryng...· 0 citations
It is shown that an optimized single-guide RNA scaffold architecture improves RNP stability, and when combined with additional EV engineering leads to a three-hundred-fold increase in potency, enabling efficient base editing or knockout in primary cells, human brain organoids and in vivo, including the mouse brain.
Xiuming Liang, Houze Zhou, Z. Nizamudeen et al.· bioRxiv· 0 citations
A therapeutic dose-response relationship linking NT-501–derived CNTF levels to JAK/STAT3 activation and photoreceptor protection in human retinal tissue is established, and an optimal concentration range for efficacy is suggested.
Yasuaki Iwama, Leia Laughlin, S. Harkins-Perry et al.· bioRxiv· 0 citations
