{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:56:13Z","timestamp":1787032573072,"version":"build-2736575974"},"posted":{"date-parts":[[2026,5,25]]},"group-title":"Molecular Biology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The intracellular delivery of therapeutic macromolecules remains a major challenge in biomedicine. Here we reconstitute the\n                  <jats:italic>Drosophila melanogaster<\/jats:italic>\n                  Arc1 (dArc1) retroelement-derived capsid entirely from purified recombinant protein components and in vitro transcribed RNA, creating a fully defined, cell-free assembled protein nanoparticle system. Through affinity engineering of the dArc1 RNA-binding domain, we enable efficient encapsulation of mRNA payloads and Cas9 ribonucleoproteins. Unexpectedly, we discover that dArc1 capsids bind mammalian cells through a direct interaction with the surface receptor SORCS2. Leveraging this interaction, we show that intramuscular injection of dArc1 capsids carrying Cas9 gene editors achieves up to 18% exon skipping and restores dystrophin expression in muscle fibers of mdx mice, a model of Duchenne muscular dystrophy. Enhanced delivery efficiency in regenerating and dystrophic muscle correlates with upregulated SORCS2 expression, supporting our finding that SORCS2 facilitates cellular uptake of dArc1 capsids. This work demonstrates the potential of in vitro-assembled protein nanoparticles for delivery of molecular cargoes.\n                <\/jats:p>","DOI":"10.64898\/2026.05.25.727180","type":"posted-content","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T16:40:16Z","timestamp":1779727216000},"source":"Crossref","is-referenced-by-count":1,"title":["In vitro\u2013reconstituted Drosophila Arc capsids deliver gene editors to dystrophic muscle"],"prefix":"10.64898","author":[{"given":"Blake","family":"Lash","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute; Cambridge, MA, USA"},{"name":"Yang Tan Collective; Cambridge, MA, USA"},{"name":"McGovern Institute for Brain Research at MIT; Cambridge, MA, USA"},{"name":"Broad Institute of MIT and Harvard; Cambridge, MA, USA"},{"name":"Department of Brain and Cognitive Science, Massachusetts Institute of Technology; Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Strebinger","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute; 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