文献类型： 外文期刊

作者： Ban, Qian ¹ ; Lee, Junseok ² ; Shi, Zhenni ¹ ; Lu, Daoqiang ³ ; Qiao, Li ¹ ; Yang, Peng ² ; Xiaofeng, L. ¹ ; Cheng, Hongya ¹ ; Zhang, Meng ¹ ; Hou, Jinbin ¹ ; Yao, Jenna H. ² ; Wang, Jun ³ ; Huang, Poyi ⁵ ; Tseng, Hsian-Rong ² ; Zhu, Yazhen ² ; Chen, Li -Ching ⁶ ; Hui, Wenqiao ⁷ ; Liu, Dahai ³ ;

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

2.Univ Calif Los Angeles, Calif Nanosyst Inst CNSI, Crump Inst Mol Imaging CIMI, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

3.Foshan Univ, Sch Med, Foshan 528000, Guangdong, Peoples R China

4.Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing 210096, Peoples R China

5.AlbCura Corp Inc, Taipei 248022, Taiwan

6.Cathay Gen Hosp, Dept Obstet & Gynecol, Taipei 106, Taiwan

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

关键词： ?-Hemoglobinopathies; Intraosseous injection; Hematopoietic stem cells; Knock -in; HBB gene; Nonviral vectors

期刊名称：NANO TODAY （ 影响因子：18.962； 五年影响因子：20.24 ）

ISSN： 1748-0132

年卷期： 2022 年 47 卷

页码：

收录情况： SCI

摘要： beta-Hemoglobinopathies are hereditary diseases originating from mutations in the hemoglobin beta (HBB) gene. Allogeneic transplantation of hematopoietic stem cells (HSCs) is the only approved treatment to date providing a cure, which is limited due to low histocompatibility from potential donors. Although several clinical trials are introducing the functional HBB gene into autologous HSCs, the ex vivo viral transfection method raises safety concerns for clinical translation. Here, we reported a novel strategy that features direct bone marrow delivery of a CRISPR/Cas9-mediated knock-in system that integrates a copy of the functional HBB gene to the genome by supramolecular nanoparticle (SMNP) nonviral vectors. We demonstrated the feasibility of SMNP vectors for the delivery of the knock-in system. First, the biodistribution of SMNPs was monitored after intraosseous (i.o.) injection in a mouse model. Second, the in vitro CRISPR/Cas9-mediated knock-in of the HBB/GFP gene via SMNP vectors was evaluated in mouse stem cells. Finally, in vivo CRISPR/ Cas9-mediated knock-in of mouse hematopoietic stem and progenitor cells (HSPCs) was performed by i.o. injection of SMNP vectors into mouse bone marrow. We believe this strategy presents a unique and in-novative approach to treating beta-hemoglobinopathies.(c) 2022 Published by Elsevier Ltd.