Worthington Atesh K, Borges Beltran, Lum Tony, Echeverri Elisa Schrader, Zada Fareha Moulana, Cordero Marco A, Kim Hyejin, Zenhausern Ryan, Celik Ozgenur, Shaw Cindy, Gutierrez-Martinez Paula, Omarova Marzhana, Blanchard Chris, Burns Sean, Cromer M Kyle, Dahlman James E, MacKenzie Tippi C
Department of Surgery, University of California, San Francisco, CA, USA.
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA.
bioRxiv. 2025 May 12:2025.05.12.652147. doi: 10.1101/2025.05.12.652147.
genome editing for hematologic malignancies is limited by inefficient delivery of genome editors to hematopoietic stem cells (HSC) in the bone marrow. To overcome this limitation, we capitalized on the inherent liver tropism of lipid nanoparticles (LNPs) and the liver niche of fetal HSCs. We demonstrate that delivery of LNPs without active targeting ligands to the fetal liver results in potentially therapeutic levels of HSC editing.
用于血液系统恶性肿瘤的基因组编辑受到基因组编辑器向骨髓中造血干细胞（HSC）递送效率低下的限制。为了克服这一限制，我们利用了脂质纳米颗粒（LNP）固有的肝脏嗜性和胎儿造血干细胞的肝脏微环境。我们证明，在没有活性靶向配体的情况下将LNP递送至胎儿肝脏可实现具有潜在治疗水平的造血干细胞编辑。
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