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It is usually caused by meiotic arrest with genetic variants and is difficult to treat via drugs or surgery. mRNA\u2010lipid nanoparticle (LNP) delivery is a promising therapeutic option for maturation arrest with monogenic variants via protein replacement therapy. Herein, a spermatocytes\u2010tropic LNP (Pool1\u2010LNP3) was identified via a library of 30 ionizable lipids screening. And in vivo delivery of this novel LNP composition using rete testis microinjection was shown to be high spermatocytes targeting with high transfection efficiency. Thereafter, it was revealed that in vivo delivery of Pool1\u2010LNP3 encapsulating\n                    <jats:italic>Msh5<\/jats:italic>\n                    mRNA could promote crossover formation and restore spermatogenesis in\n                    <jats:italic>\n                      Msh5\n                      <jats:sup>D486Y\/D486Y<\/jats:sup>\n                    <\/jats:italic>\n                    mouse models with DNA double\u2010strand break (DSB) recombination defects. Notably, the offspring without genomic integration was born using intracytoplasmic sperm injection (ICSI) derived from the rescue of\n                    <jats:italic>\n                      Msh5\n                      <jats:sup>D486Y\/D486Y<\/jats:sup>\n                    <\/jats:italic>\n                    mouse and embryo transfer. In addition, it was demonstrated that\n                    <jats:italic>Maps<\/jats:italic>\n                    mRNA\u2010LNP3 recovered spermatogenesis in\n                    <jats:italic>Maps<\/jats:italic>\n                    KO mouse with meiotic arrest. Altogether, these findings suggested that this spermatocyte\u2010tropic mRNA\u2010LNP delivery could become a viable and applicable strategy for the treatment of spermatogenic disorders with genetic defects, providing a foundation for future clinical application.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509855","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:16:12Z","timestamp":1770804972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Testicular mRNA\u2010LNP Delivery: A Novel Therapy for Genetic Spermatogenic Disorders"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9186-7125","authenticated-orcid":false,"given":"Chenwang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Andrology the Center for Men's Health Urologic Medical Center Reproductive Medicine Center Shanghai Key Laboratory of 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