文献类型： 外文期刊

作者： Cheng, Hongya ¹ ; Hui, Wenqiao ² ; Kang, Hanyue ³ ; Shi, Zhenni ¹ ; Liu, Jianlei ⁴ ; Wang, Xin ¹ ; Qi, Fei ⁵ ; Mao, Lin ¹ ; Ding, Huiqian ¹ ; Hu, Rongjian ¹ ; Begum, Nabila ⁶ ; Lu, Daoqiang ⁶ ; Chen, Dandan ¹ ; Cheng, Xinyue ¹ ; Wan, Miaomiao ¹ ; Liu, Dahai ⁷ ; Tseng, Hsian-Rong ⁸ ; Ye, Shoudong ¹ ; Xu, Xiaobin ³ ; Zhang, Baowei ¹ ; Ban, Qian ¹ ;

作者机构： 1.Anhui Univ, Ctr Stem Cell & Translat Med, Sch Life Sci, Hefei 230601, Anhui, Peoples R China

2.Anhui Acad Agr Sci, Inst Anim Husb & Vet Med, Anhui Prov Key Lab Livestock & Poultry Prod Safety, Hefei 230031, Peoples R China

3.Tongji Univ, Sch Mat Sci & Engn, Key Lab Adv Civil Engn Mat Minist Educ, Key Lab D&A&A Met Funct Mat, Shanghai 201804, Peoples R China

4.Foshan Fosun Chancheng Hosp, Foshan 528000, Peoples R China

5.Anhui Med Coll, Sch Clin Med, Hefei 230601, Anhui, Peoples R China

6.Foshan Univ, Sch Med, Foshan 528000, Peoples R China

7.Foshan Univ, Sch Anim Sci & Technol, Guangdong Prov Key Lab Anim Mol Design & Precise B, Foshan 528231, Guangdong, Peoples R China

8.Univ Calif Los Angeles, Calif Nano Syst Inst CNSI, Crump Inst Mol Imaging CIMI, David Geffen Sch Med,Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

9.Fudan Univ, Ctr Micro Nano Syst, Sch Informat Sci & Technol SIST, Shanghai 200433, Peoples R China

关键词： Nanosubstrate; Nanoparticle; CBE3; BCL11A; HBG; Gene therapy

期刊名称：NANO TODAY （ 影响因子：10.9； 五年影响因子：13.3 ）

ISSN： 1748-0132

年卷期： 2025 年 61 卷

页码：

收录情况： SCI

摘要： Here, we developed and demonstrated a novel integrative system-Silica Nanorods (SNA) substrate cell capture combined with Supramolecular Nanoparticle (SMNP) delivery mediated CBE base editing (SNA & sdot;SMNP & sdot;CBE)- achieving the synchronization of CD34+HSPCs cell capture and gene editing for beta-hemoglobinopathies. First, in vitro study shows it enables efficient and precise modification of BCL11A promoter in CD34+HSPCs, yielding the highly editing efficiency of 50.4 %, thus making an alternative strategy to conventional immunomagnetic cell separation and electroporation transfection system mediated CBE editing (IMS & sdot;EP & sdot;CBE). Then, we transplanted the edited human CD34+HSPCs into severe combined immunodeficiency (SCID) mice by using intraosseous injection strategy. When compared with conventional IMS & sdot;EP & sdot;CBE methods, our results showed that significantly higher human HBG expression in the bone marrow and peripheral blood of recipient mice, and long-term engraftment, evidenced from similar gene expression profiles to na & iuml;ve CD34+HSPCs at 14 weeks. Conclusively, our integrative system-SNA & sdot;SMNP & sdot;CBE & sdot;intraosseous injection-offers an appealing novel way for the unique potential of gene therapy in the clinic application for beta-hemoglobinopathies patients.