ArticleNature biomedical engineering2025
Safer and efficient base editing and prime editing via ribonucleoproteins delivered through optimized lipid-nanoparticle formulations.
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Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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68citing papers in PubMed, 1 pooled it
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Non-Viral CRISPR carriers: transient delivery with lasting effects.Drug delivery · 2026Review
- Efficient PE system PE7-scFv-MLH1dn by optimizing the configuration of La and MLH1dn.Synthetic and systems biotechnology · 2026Article
- CRISPR RNP-Mediated Transgene-Free Genome Editing in Plants: Advances, Challenges and Future Directions for Tree Species.Plant, cell & environment · 2026Review
- Editing around the target: epitope engineering to protect stem cell grafts.Blood advances · 2026Review
- Chemically modified CRISPR enzymes for multi-organ genome editingbioRxiv : the preprint server for biology · 2026Article
- Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.Nature biomedical engineering · 2026Article
- CRISPR-Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases.Clinical and translational medicine · 2026Review
- Transgene-free genome editing in plants.aBIOTECH · 2026Review
- Advances in vehicles for in situ delivery: From classical vectors to biologically inspired structures.Synthetic and systems biotechnology · 2026Review
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Recent Advances in Non-Viral Vectors for Gene Therapy and Gene Delivery: From Lipid Nanoparticles to Engineered Extracellular Vesicles.Pharmaceutics · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Structure-guided engineering of AI-derived adenine base editors for nuclear and mitochondrial DNA editing.Nucleic acids research · 2026Article
- Efficient in vivo cytosine base editing using virus-like particles with uracil DNA glycosylase inhibition.Nature biotechnology · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Engineered transformer base editor with unconstrained PAM requirements.Molecular therapy. Nucleic acids · 2026Article
- Review
- Prime editing in neuropsychiatric disorders: From mutation-specific target selection to clinical translation.Neuroprotection (Chichester, England) · 2026Review
- Prime editing updates: technological evolution, methodological expansion, and delivery strategies for in vivo applications.BMB reports · 2026Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Rafał Hołubowicz *Gavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Samuel W Du *Gavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.ORCID 0000-0002-9655-3659
Jiin Felgner *Adeline Yen Mah Vaccine Center, Department of Physiology and Biophysics, University of California, Irvine, CA, USA.
Roman SmidakGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Elliot H ChoiGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Grazyna PalczewskaGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Carolline Rodrigues MenezesGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Zhiqian DongGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.ORCID 0000-0002-8748-4532
Fangyuan GaoGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Omar MedaniGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Alexander L YanGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.ORCID 0000-0002-8594-7994
Maria W HołubowiczGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Paul Z ChenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Marco BassettoGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
Eleonora RisalitiGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.
David SalomGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.ORCID 0000-0002-3208-1509
J Noah WorkmanDepartment of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-0921-1803
Philip D KiserGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA.ORCID 0000-0003-1184-9539
Andrzej T FoikInternational Centre for Translational Eye Research (ICTER), Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland.ORCID 0000-0003-1110-9223
David C LyonDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID 0000-0002-9943-7557
Philip L FelgnerAdeline Yen Mah Vaccine Center, Department of Physiology and Biophysics, University of California, Irvine, CA, USA. pfelgner@hs.uci.edu.ORCID 0000-0002-4117-8505
Krzysztof PalczewskiGavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, USA. kpalczew@uci.edu.ORCID 0000-0002-0788-545X
Funding
Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9MCenter for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7MSTRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0MAdjuvant Comparison and Characterization in Influenza , Chlamydia muridarum, and Coxiella burnetii Vaccines75N93022C00054 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI FELGNER, PHILIP · 2022 to 2025
$10.2MMEDICAL SCIENTIST TRAINING PROGRAMT32GM008620 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLDIN, ALAN L · 1999 to 2023
$8.1MIntegrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4MPrecision genome editing in vivo to treat retinal diseasesR01EY034501 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Audrone Lapinaite, Krzysztof Palczewski · 2023 to 2026
$3.9MNEI UCI Center Core Grant for Vision ResearchP30EY034070 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Vladimir Jivkov Kefalov · 2022 to 2026
$3.7MThe complex role of phosphodiesterase 6 in rod photoreceptor health and functionR01EY030873 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Krzysztof Palczewski · 2020 to 2026
$3.5MPredoctoral Training Program in Human GeneticsT32GM148383 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Kimberly F Doheny, ANDREW S MCCALLION · 2023 to 2026
$2.4MRetinal sheet transplant impact on functional organization of visual cortex in retinal degenerate animal modelsR01EY032948 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LYON, DAVID C, SEILER, MAGDALENE J · 2022 to 2025
$2.3MDelivery Technologies for In Vivo Genome EditingUG3AI150551 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2019 to 2021
$2.3MBLRD VA I01 BX004939Fundacja na rzecz Nauki Polskiej (Foundation for Polish Science) FENG.02.01-IP.05-T005/23Narodowe Centrum Nauki (National Science Centre) 2022/47/B/NZ5/03023, 2020/39/D/NZ4/01881, 2019/34/E/NZ5/00434NCI NIH HHS P30 CA062203NEI NIH HHS F30 EY033642NEI NIH HHS P30 EY034070NEI NIH HHS R01 EY009339NEI NIH HHS R01 EY030873NEI NIH HHS R01 EY032948NEI NIH HHS R01 EY034501NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R00 HL163805NIAID NIH HHS 75N93022C00054NIAID NIH HHS U01 AI142756NIAID NIH HHS UG3 AI150551NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM008620NIGMS NIH HHS T32 GM148383NINDS NIH HHS R21 NS113264United States Department of Defense | Defense Threat Reduction Agency (DTRA) N66001-21-C-4013U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30EY034070U.S. Department of Health & Human Services | National Institutes of Health (NIH) R00HL163805U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01EY009339, R01EY030873, P30EY034070, P30CA062203U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01EY032948, R21NS113264U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM008620, F30EY033642U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM148383U.S. Department of Health & Human Services | National Institutes of Health (NIH) UG3AI150551, U01AI142756, R35GM118062, RM1HG009490U.S. Department of Veterans Affairs (Department of Veterans Affairs) I01BX004939
Abstract
Delivering ribonucleoproteins (RNPs) for in vivo genome editing is safer than using viruses encoding for Cas9 and its respective guide RNA. However, transient RNP activity does not typically lead to optimal editing outcomes. Here we show that the efficiency of delivering RNPs can be enhanced by cell-penetrating peptides (covalently fused to the protein or as excipients) and that lipid nanoparticles (LNPs) encapsulating RNPs can be optimized for enhanced RNP stability, delivery efficiency and editing potency. Specifically, after screening for suitable ionizable cationic lipids and by optimizing the concentration of the synthetic lipid DMG-PEG 2000, we show that the encapsulation, via microfluidic mixing, of adenine base editor and prime editor RNPs within LNPs using the ionizable lipid SM102 can result in in vivo editing-efficiency enhancements larger than 300-fold (with respect to the delivery of the naked RNP) without detectable off-target edits. We believe that chemically defined LNP formulations optimized for RNP-encapsulation stability and delivery efficiency will lead to safer genome editing.
Indexed as
Gene EditingLipidsNanoparticlesRibonucleoproteinsAnimalsCell-Penetrating PeptidesCRISPR-Cas SystemsHEK293 CellsHumansLiposomesMiceCell-Penetrating PeptidesLipid NanoparticlesLipidsLiposomesRibonucleoproteins
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