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We have previously reported an entirely synthetic gold nanoparticle formulation which can safely and effectively deliver multiple different CRISPR systems as ribonucleoprotein (RNP) into hematopoietic stem cells and immune cells. Here, we describe a modified version of this nanoparticle to simultaneously deliver CRISPR Cas9 RNP and transgene\u2010encoding DNA templates (HDT) as long as\u2009~2.1\u2009kb. We evaluate this HDT\u2010CRISPR\u2010AuNP for gene editing at two loci of interest with different transgene cargo. These nanoparticles successfully deliver gene editing into primary human T cells and hematopoietic stem and progenitor cells with insertion of an antigen\u2010specific T cell receptor transgene. This proof\u2010of\u2010concept immune engineering study demonstrates a simple, synthetic nanoformulation for co\u2010delivery of all cargo required for CRISPR\u2010mediated delivery of transgene cassettes with potential for efficacy in vivo.<\/jats:p>","DOI":"10.1002\/anbr.202500242","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:59:43Z","timestamp":1775012383000},"source":"Crossref","is-referenced-by-count":5,"title":["Nonviral Gold Nanoparticle\u2010Mediated Delivery of CRISPR\u2010Cas9 Ribonucleoprotein and Long DNA Transgenes Into Primary Blood Cells"],"prefix":"10.1002","volume":"6","author":[{"given":"Rachel A.","family":"Cunningham","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikeya S. 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