{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:08:41Z","timestamp":1788955721676,"version":"build-2803163510"},"posted":{"date-parts":[[2026,1,13]]},"group-title":"Bioengineering","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"crossref","award":["1R21HL173710-01"],"award-info":[{"award-number":["1R21HL173710-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006227","name":"Lawrence Livermore National Laboratory","doi-asserted-by":"crossref","award":["DE-AC52-07NA27344"],"award-info":[{"award-number":["DE-AC52-07NA27344"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/038321296","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Genome editing enzymes have vast therapeutic potential. However, achieving sufficient delivery\n                  <jats:italic>in vivo<\/jats:italic>\n                  remains a major challenge, because editing machinery is confined to the subset of transfectable cells in a tissue. Here, we tested the possibility that genome editing could be amplified\n                  <jats:italic>in vivo<\/jats:italic>\n                  by enabling transfected cells to transfer editing enzymes to neighboring cells. Our data show that this NANoparticle-Induced Transfer of Enzyme (NANITE) strategy quadrupled editing efficiency in cultured cells relative to non-spreading controls. A single intravenous injection of the NANITE plasmid into mice induced \u223c3-fold higher levels of liver editing at the transthyretin (\n                  <jats:italic>Ttr<\/jats:italic>\n                  ) locus relative to non-spreading controls, with corresponding reductions in serum TTR levels. Spreading therapeutic enzymes offers a nonviral and non-infectious strategy to boost therapeutic effects after delivery.\n                <\/jats:p>","DOI":"10.64898\/2026.01.13.699115","type":"posted-content","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:30:18Z","timestamp":1768368618000},"source":"Crossref","is-referenced-by-count":1,"title":["Amplified genome editing by\n                  <i>in vivo<\/i>\n                  editor production"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5755-2303","authenticated-orcid":false,"given":"Wayne","family":"Ngo","sequence":"first","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Gladstone Institute of Data Science and Biotechnology; San Francisco, CA, USA"},{"name":"California Institute for Quantitative Biosciences, University of California, Berkeley; Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rosas-Rivera","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Gladstone Institute of Data Science and Biotechnology; San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Wasko","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco; San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Hyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaan","family":"Gogna","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingkun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Gladstone Institute of Data Science and Biotechnology; San Francisco, CA, USA"},{"name":"California Institute for Quantitative Biosciences, University of California, Berkeley; Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason T.","family":"Hooks","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Gladstone Institute of Data Science and Biotechnology; San Francisco, CA, USA"},{"name":"California Institute for Quantitative Biosciences, University of California, Berkeley; Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Gladstone-UCSF Institute of Genomic Immunology; San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9161-999X","authenticated-orcid":false,"given":"Jennifer A.","family":"Doudna","sequence":"additional","affiliation":[{"name":"Innovative Genomics Institute; University of California, Berkeley; Berkeley CA, USA"},{"name":"Gladstone Institute of Data Science and Biotechnology; San Francisco, CA, USA"},{"name":"California Institute for Quantitative Biosciences, University of California, Berkeley; Berkeley, CA, USA"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA, USA"},{"name":"Gladstone-UCSF Institute of Genomic Immunology; San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026090904450947000_2026.01.13.699115v3.1","first-page":"1","article-title":"Targeted delivery of genome editors in vivo","volume":"44","year":"2026","journal-title":"Nat. Biotechnol."},{"key":"2026090904450947000_2026.01.13.699115v3.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10235-x"},{"key":"2026090904450947000_2026.01.13.699115v3.3","doi-asserted-by":"crossref","first-page":"eadk3920","DOI":"10.1126\/scitranslmed.adk3920","article-title":"In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene","volume":"17","year":"2025","journal-title":"Sci. Transl. Med"},{"key":"2026090904450947000_2026.01.13.699115v3.4","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1182\/blood-2022-169120","article-title":"Engineered Stem Cell Antibody Paired Evasion 1 (ESCAPE-1): Paired HSC Epitope Engineering and Upregulation of Fetal Hemoglobin for Antibody-Mediated Autologous Hematopoietic Stem Cell Therapy Conditioning for the Treatment of Hemoglobinopathies","volume":"140","year":"2022","journal-title":"Blood"},{"key":"2026090904450947000_2026.01.13.699115v3.5","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"2026090904450947000_2026.01.13.699115v3.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093133"},{"key":"2026090904450947000_2026.01.13.699115v3.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.06.013"},{"key":"2026090904450947000_2026.01.13.699115v3.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature20607"},{"key":"2026090904450947000_2026.01.13.699115v3.9","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1038\/s41467-026-72072-w","article-title":"Non-destructive transcriptomics via vesicular export","volume":"17","year":"2026","journal-title":"Nat. Commun"},{"key":"2026090904450947000_2026.01.13.699115v3.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14977-8"},{"key":"2026090904450947000_2026.01.13.699115v3.11","doi-asserted-by":"publisher","DOI":"10.1101\/2022.12.26.521940"},{"key":"2026090904450947000_2026.01.13.699115v3.12","doi-asserted-by":"publisher","DOI":"10.1101\/2025.10.21.683747"},{"key":"2026090904450947000_2026.01.13.699115v3.13","doi-asserted-by":"crossref","first-page":"e2313009120","DOI":"10.1073\/pnas.2313009120","article-title":"In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma","volume":"120","year":"2023","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2026090904450947000_2026.01.13.699115v3.14","doi-asserted-by":"crossref","first-page":"eadu2085","DOI":"10.1126\/scitranslmed.adu2085","article-title":"Computationally designed mRNA-launched protein nanoparticle immunogens elicit protective antibody and T cell responses in mice","volume":"17","year":"2025","journal-title":"Sci. Transl. Med"},{"key":"2026090904450947000_2026.01.13.699115v3.15","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.11.575257"},{"key":"2026090904450947000_2026.01.13.699115v3.16","first-page":"1","article-title":"In vivo human T cell engineering with enveloped delivery vehicles","volume":"42","year":"2023","journal-title":"Nat. Biotechnol"},{"key":"2026090904450947000_2026.01.13.699115v3.17","doi-asserted-by":"crossref","unstructured":"Hamilton, J. R. et al. Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering. Cell Reports 35, 109207 (2021).","DOI":"10.1016\/j.celrep.2021.109207"},{"key":"2026090904450947000_2026.01.13.699115v3.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2413519121"},{"key":"2026090904450947000_2026.01.13.699115v3.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.021"},{"key":"2026090904450947000_2026.01.13.699115v3.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-02078-y"},{"key":"2026090904450947000_2026.01.13.699115v3.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7297"},{"key":"2026090904450947000_2026.01.13.699115v3.22","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300745"},{"key":"2026090904450947000_2026.01.13.699115v3.23","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab634"},{"key":"2026090904450947000_2026.01.13.699115v3.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2013.01.011"},{"key":"2026090904450947000_2026.01.13.699115v3.25","doi-asserted-by":"crossref","first-page":"eado2054","DOI":"10.1126\/sciimmunol.ado2054","article-title":"Trogocytosis of chimeric antigen receptors between T cells is regulated by their transmembrane domains","volume":"10","year":"2025","journal-title":"Sci. Immunol."},{"key":"2026090904450947000_2026.01.13.699115v3.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-026-01920-0"},{"key":"2026090904450947000_2026.01.13.699115v3.27","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0412-0"},{"key":"2026090904450947000_2026.01.13.699115v3.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-01000-4"},{"key":"2026090904450947000_2026.01.13.699115v3.29","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(17)37680-9"},{"key":"2026090904450947000_2026.01.13.699115v3.30","doi-asserted-by":"crossref","unstructured":"Catalano, M. & O\u2019Driscoll, L . Inhibiting extracellular vesicles formation and release: a review of EV inhibitors. J. Extracell. Vesicles 9, 1703244 (2020).","DOI":"10.1080\/20013078.2019.1703244"},{"key":"2026090904450947000_2026.01.13.699115v3.31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153124"},{"key":"2026090904450947000_2026.01.13.699115v3.32","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(19)47429-2"},{"key":"2026090904450947000_2026.01.13.699115v3.33","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1016-8478(23)13317-6","article-title":"Colchicine Activates Actin Polymerization by Microtubule Depolymerization","volume":"7","year":"1997","journal-title":"Mol. Cells"},{"key":"2026090904450947000_2026.01.13.699115v3.34","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-011-9208-4"},{"key":"2026090904450947000_2026.01.13.699115v3.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01436-z"},{"key":"2026090904450947000_2026.01.13.699115v3.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40788-8"},{"key":"2026090904450947000_2026.01.13.699115v3.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(97)00144-2"},{"key":"2026090904450947000_2026.01.13.699115v3.38","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/s41564-023-01389-9","article-title":"Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies","volume":"8","year":"2023","journal-title":"Nat. Microbiol"},{"key":"2026090904450947000_2026.01.13.699115v3.39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001110"},{"key":"2026090904450947000_2026.01.13.699115v3.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03432-4"},{"key":"2026090904450947000_2026.01.13.699115v3.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.07.009"},{"key":"2026090904450947000_2026.01.13.699115v3.42","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1016\/j.ymthe.2025.04.027","article-title":"Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library","volume":"33","year":"2025","journal-title":"Mol. Ther"},{"key":"2026090904450947000_2026.01.13.699115v3.43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-010181"},{"key":"2026090904450947000_2026.01.13.699115v3.44","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz148"},{"key":"2026090904450947000_2026.01.13.699115v3.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.014"},{"key":"2026090904450947000_2026.01.13.699115v3.46","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107454"},{"key":"2026090904450947000_2026.01.13.699115v3.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-025-02556-5"},{"key":"2026090904450947000_2026.01.13.699115v3.48","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300314"},{"key":"2026090904450947000_2026.01.13.699115v3.49","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7701119"},{"key":"2026090904450947000_2026.01.13.699115v3.50","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300947"},{"key":"2026090904450947000_2026.01.13.699115v3.51","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jgm.1041","article-title":"Delivery and long term expression of a 135 kb LDLR genomic DNA locus in vivo by hydrodynamic tail vein injection","volume":"9","year":"2007","journal-title":"J. Gene Med"},{"key":"2026090904450947000_2026.01.13.699115v3.52","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300399"},{"key":"2026090904450947000_2026.01.13.699115v3.53","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302231"},{"key":"2026090904450947000_2026.01.13.699115v3.54","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.3.1435-1443.1995"},{"key":"2026090904450947000_2026.01.13.699115v3.55","doi-asserted-by":"crossref","unstructured":"Suhr, O. B. et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J. Rare Dis. 10, 109 (2015).","DOI":"10.1186\/s13023-015-0326-6"},{"key":"2026090904450947000_2026.01.13.699115v3.56","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.178"},{"key":"2026090904450947000_2026.01.13.699115v3.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01680-8"},{"key":"2026090904450947000_2026.01.13.699115v3.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0669-6"},{"key":"2026090904450947000_2026.01.13.699115v3.59","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6967"},{"key":"2026090904450947000_2026.01.13.699115v3.60","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0594"},{"key":"2026090904450947000_2026.01.13.699115v3.61","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku936"},{"key":"2026090904450947000_2026.01.13.699115v3.62","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-4939-9170-9_3","article-title":"Rapid Quantitative Evaluation of CRISPR Genome Editing by TIDE and TIDER","volume":"1961","year":"2019","journal-title":"Methods Mol. Biol. (Clifton, NJ)"},{"key":"2026090904450947000_2026.01.13.699115v3.63","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-03-01030.1994"},{"key":"2026090904450947000_2026.01.13.699115v3.64","doi-asserted-by":"crossref","unstructured":"Kanefuji, T. et al. Hemodynamics of a hydrodynamic injection. Mol. Ther. - Methods Clin. Dev. 1, 14029 (2014).","DOI":"10.1038\/mtm.2014.29"},{"key":"2026090904450947000_2026.01.13.699115v3.65","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0338-9"},{"key":"2026090904450947000_2026.01.13.699115v3.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02437-3"},{"key":"2026090904450947000_2026.01.13.699115v3.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01765-4"},{"key":"2026090904450947000_2026.01.13.699115v3.68","doi-asserted-by":"crossref","unstructured":"Hong, K. U. et al. A highly sensitive and accurate method to quantify absolute numbers of c-kit+ cardiac stem cells following transplantation in mice. Basic Res. Cardiol. 108, 346 (2013).","DOI":"10.1007\/s00395-013-0346-0"},{"key":"2026090904450947000_2026.01.13.699115v3.69","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu048"},{"key":"2026090904450947000_2026.01.13.699115v3.70","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0032-3"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.13.699115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:45:23Z","timestamp":1788954323000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.01.13.699115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":70,"URL":"https:\/\/doi.org\/10.64898\/2026.01.13.699115","relation":{},"subject":[],"published":{"date-parts":[[2026,1,13]]},"subtype":"preprint"}}