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CAR\u2010NK cell therapies provide innate cytotoxicity with antigen\u2010independent targeting, reducing safety risks while improving therapeutic efficacy. However, efficient genomic engineering and large\u2010scale production of allogeneic NK cells remain significant obstacles. To address these challenges, a novel microfluidic gene delivery platform is developed, the Y\u2010hydroporator, designed for allogeneic NK cell immunotherapy. This platform features a Y\u2010shaped microchannel where NK cells experience rapid hydrodynamic stretching near the stagnation point, creating transient membrane discontinuities that facilitate the uptake of exogenous cargo. The Y\u2010hydroporator achieves high delivery and transfection efficiency, processing \u22482 \u00d7 10\n                    <jats:sup>6<\/jats:sup>\n                    cells min\n                    <jats:sup>\u22121<\/jats:sup>\n                    while maintaining long\u2010term cell viability (&gt;89%) and functionality. Using this platform, human primary CAR\u2010NK cells and NKG2A\u2010knockout NK cells are successfully generated by delivering anti\u2010CD19 CAR mRNA and CRISPR\/Cas9 ribonucleoproteins, respectively. These engineered NK cells demonstrated enhanced cytotoxicity, underscoring the potential of the Y\u2010hydroporator as a transformative tool for advancing allogeneic NK cell\u2010based immunotherapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202412544","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:53:33Z","timestamp":1741726413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Advancing Allogeneic NK Cell Immunotherapy through Microfluidic Gene Delivery"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8764-9157","authenticated-orcid":false,"given":"Hyelee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Bioengineering Korea University  Seoul 02841 Republic of Korea"},{"name":"Interdisciplinary Program in Precision Public Health (PPH) Korea University  Seoul 02841 Republic of 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