Ultrasound‐Actuated Gene Editing in Human Kidney Organoids
Open accessAbstract
Efficient delivery of gene editing ribonucleoproteins (RNPs) into the interior of solid tissues remains a key hurdle to the clinical translation of non‐viral CRISPR‐Cas9 technologies. Here, we report acoustically‐actuated peptide nanoemulsions (NPeps) that can be spatiotemporally guided and activated by ultrasound to ballistically deliver RNPs into cells within the bulk of dense 3D cellular structures. Using human kidney organoids as a model, we demonstrate NPep vectors improve the spatial profile of gene editing in the organoid mass relative to commercial lipofection reagents, without disruption of tissue structure or qualitative viability features. This technologic paradigm is poised to advance imaging‐guided, deep tissue RNP delivery modalities to expand the clinical diagnostic and therapeutic potential of CRISPR‐Cas9 editing strategies.
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Cites
Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease
Ramli, M. N. B., Lim, Y. S., Koe, C. T., Demircioglu, D., Tng, W., Gonzales, K. A. U., Tan, C. P., Szczerbinska, I., Liang, H., Soe, E. L., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.06.010 · Cited by 278 · see citing works
Laperrousaz, B., Porte, S., Gerbaud, S., Härmä, V., Kermarrec, F., Hourtane, V., Bottausci, F., Gidrol, X., & Picollet-D’hahan, N. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky030 · Cited by 54 · cited 3× · see citing works
“To circumvent this, organoids are often dissociated into single cells or cell clusters, non-virally transfected, and then re-embedded into solid media [ 9, 10 ].”
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- Authors
- Miller, M. A., Vo, N., Utkarsh, Sokirniy, I., Pritchard, J., Freedman, B. S., & Medina, S. H.
- Affiliations
- Pennsylvania State University (US)
- University of Washington (US)
- Corresponding author
- Medina, Scott H.
- ORCID
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2026-06-15
- Volume
- 13
- Issue
- 49
- Pages
- e20402-e20402
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC13336553
- OpenAlex
- W7164842802
- Cited by
- 0
- References
- 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation (R21DK128638, R35GM142902, U01DK127553, U01AI176460)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- CRISPR/Cas9 ribonucleoprotein, kidney organoids
- MeSH terms
- Gene Editing, Humans, Kidney, Organoids, Ribonucleoproteins, CRISPR-Cas Systems
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