Superior COL7A1 and TGM1 gene expression in difficult-to-transfect skin cell mediated by highly branched poly( β-amino esters) through stepwise fractionation

被引:1
作者
Pan, Chaolan [1 ]
Wang, Chenfei [1 ]
Zhao, Yitong [2 ]
Bo, Tao [3 ]
Han, Liping [3 ,4 ]
Yao, Dingjin [5 ]
Wang, Yumeng [1 ]
Wang, Xiaoxiao [6 ]
Shi, Linjing [7 ]
Zhao, Anqi [1 ]
Cao, Qiaoyu [1 ]
Chen, Fuying [1 ]
He, Wei [1 ]
Ye, Ying [1 ]
Zhang, Si [3 ]
Li, Ming [1 ]
机构
[1] Fudan Univ, Natl Childrens Med Ctr, Dept Dermatol, Childrens Hosp, Shanghai 201102, Peoples R China
[2] Anhui Univ Sci & Technol, Sch Med, Huainan 232000, Anhui, Peoples R China
[3] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, NHC Key Lab Glycoconjugate Res, Shanghai 200032, Peoples R China
[4] Fudan Univ, Huashan Hosp, Dept Blood Transfus, Shanghai, Peoples R China
[5] Shanghai EditorGene Technol Co Ltd, Shanghai 200000, Peoples R China
[6] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Dermatol, Sch Med, Shanghai 200092, Peoples R China
[7] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Dermatol, Xian 710061, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
Gene therapy; Gene transfection; Branchedpoly(beta-amino ester)s; Stepwise fractionation; POLY(BETA-AMINO ESTERS); CONGENITAL ICHTHYOSIS; LIPID NANOPARTICLES; SYSTEMIC DELIVERY; MESSENGER-RNA; GENE; POLYMERS; VII;
D O I
10.1016/j.jconrel.2024.04.030
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Delivering functional gene into targeted skin cells or tissues to modulate the genes expression, has the potential to treat various hereditary cutaneous disorders. Nevertheless, the lack of safe and effective gene delivery vehicles greatly limits the clinical translation of gene therapy for inherited skin diseases. Herein, we developed a facile elution fractionation strategy to isolate eight HPAEs with M-w ranging from 7.6 to 131.8 kg/mol and & Dstrok; < 2.0 from the one crude HPAE(23.7k), and investigated the expression efficiency for TGM1 and COL7A1 plasmids. Gene transfection results revealed that the intermediate MW HPAEs, HPAE(20.6k), exhibited the highest gene transfection efficiency (46.4%) and the strongest mean fluorescence intensity (143,032 RLU), compared to other isolated components and the crude product. Importantly, best-performing isolated HPAE effectively delivered COL7A1 (15,974 bp) and TGM1 (7181 bp) plasmids, promoting the efficient expression of type VII collagen (C7) and transglutaminase-1 proteins in cutaneous cells. Our study establishes a straightforward step-by-step elution fractionation strategy for the development of HPAEs gene delivery vectors, expediting their clinical translation in inherited skin diseases.
引用
收藏
页码:82 / 94
页数:13
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