Skip to content
Log in

Efficient genome editing in the non-human primate brain using programmable extracellular vesicles

Xiuming Liang Houze Zhou Z. Nizamudeen Eleni Kyriakopoulou Angharad E. Evans Samantha Roudi H. Y. Estupiñán J. Rädler V. W. Hou Callum D.W. Daniel Inés Hernández-Pérez Malika Singh Pardis Parsi Daniel A. Lonergan Lidia Menéndez Berlana Robert Walmsley Ying Chen Juliette S. M. T. Suermondt M. Mowoe Andre Görgens Christopher A. Smith George O. Redrup Lewis D. Ashmore Samuel Perez Kanchan J. Thapa Shrishti Banerjee Scott E. Bonner Mariana Conceicao Rebecca L. Gavin Justin Hean Peter D. Horrocks Maria O. Levitin P. Lundin Heena Sharma R. Tawar Liang Liu Dhanu Gupta D. R. Carter J. Nordin S. E. Andaloussi
Aug 2026 · bioRxiv · 0 citations
Biology

TL;DR

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.

DOI Semantic Scholar
View source

Similar papers

Review Aug 2026

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

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 · 0 citations
Review Open access Jul 2026

In vivo delivery strategies for therapeutic CRISPR genome editing

A comprehensive review of delivery modalities of CRISPR systems solely in vivo that underpin their therapeutic translation and outlines the remaining barriers to durable, tissue-selective, and broadly deployable CRISPR therapeutics is provided.

L. Martin, Jure Bohinc, Alessandra Recchia et al. · 0 citations
Open access Aug 2026

Compact 9dBEs Enable Efficient and Precise Genome Editing in Mammalian Cells and In Vivo

An efficient Cas9d system (Cas9dUltra) is developed through gRNA and protein engineering, and its base editors (9dBEs) further developed through gRNA and protein engineering, enabling efficient and precise genome editing in human cells.

Qingquan Xiao, Zhijin Tian, Luqi Weng et al. · 0 citations
Review Open access Jul 2026

Base editing for precision therapeutics.

Base editing (BE), the precise installation of single-nucleotide changes in DNA or RNA without inducing double-strand breaks, holds substantial therapeutic promise for correcting single-nucleotide variants, which constitute more than half of the known pathogenic genetic variants. Recent advances have improved base editor specificity, efficiency, and delivery, enabling clinically oriented procedures. Clinically, BE has shown early success or strong translational promise in sickle cell disease, β-thalassemia, leukemia (via CAR T and epitope engineering), hypercholesterolemia (PCSK9 and ANGPTL3), alpha-1-antitrypsin deficiency, and glycogen storage disease type Ia. Key remaining challenges include bystander editing within the activity window, residual off-target DNA and RNA editing, delivery constraints (payload size, tissue targeting, and redosing limits), immunogenicity, and the need for durable long-term safety evidence across relevant cell types and disease contexts. Continued technological refinements, careful preclinical validation, and rigorous clinical assessment will be essential to fully realize BE's transformative potential in precision medicine.

Moksada Regmi, K. Ma, C. Bi et al. · 0 citations
Review Open access Jul 2026

Nanoengineering Systems for Gene Therapy: Mechanisms, Modalities, and Future Directions

The continued convergence of nanotechnology and genome engineering may support the development of personalized medicine strategies that adapt genetic engineering tools for patient-specific applications, thereby improving the safety and reliability of gene-editing therapies.

Raheem Mais, Ayush Kumar, Armand Ahmetaj et al. · 0 citations
#gene editing Open access Aug 2026

A PepFect14 analog improves non‐viral CRISPR delivery in primary human cells to facilitate genome editing and repair

A PepFect14 analog is employed to deliver high-fidelity Cas9-ribonucleoproteins and non-viral repair templates into primary human skin cells to mediate gene editing and repair targeting genes underlying the group of genetic skin blistering disorders epidermolysis bullosa (EB).

A. du Rand, Courtney Masterson, Daniel J Verdon et al. · 0 citations