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Double-Helix Duality: Rods Bow, Toroids Wow in the Nuclease Arena

文献类型: 外文期刊

作者: Li, Yanhua 1 ; Chen, Xiyi 2 ; Tong, Changgui 1 ; Li, Lei 1 ; Qin, Chunfang 3 ; Zhang, Ming 4 ; Zhao, Yan 4 ; Chen, Qixian 3 ; Wang, Yue 4 ;

作者机构: 1.Dalian Med Univ, Hosp 2, 467 Zhongshan Rd, Dalian 116027, Peoples R China

2.Dalian Med Univ, Sch Publ Hlth, Dalian 116044, Peoples R China

3.Zhejiang Univ, Innovat Ctr Yangtze River Delta, Jiaxing 314100, Zhejiang, Peoples R China

4.Dalian Univ Technol, Dept Gastr Surg, Liaoning Canc Inst & Hosp, Canc Hosp, Shenyang 110042, Liaoning, Peoples R China

5.China Med Univ, Dept Gastr Surg, Canc Hosp, Shenyang 110042, Liaoning, Peoples R China

6.Liaoning Canc Hosp & Inst, Prov Key Lab Interdisciplinary Med Engn Gastrointe, Shenyang 110042, Liaoning, Peoples R China

7.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen 518120, Peoples R China

期刊名称:JOURNAL OF PHYSICAL CHEMISTRY LETTERS ( 影响因子:4.6; 五年影响因子:5.1 )

ISSN: 1948-7185

年卷期: 2025 年 16 卷 15 期

页码:

收录情况: SCI

摘要: Utilizing polyion complexation, the formation of rod-like DNA condensates is driven by the intrinsic rigidity of supramolecular plasmid DNA. Upon interaction with polycationic block copolymers of poly(ethylene glycol)-polylysine (PEG-PLys), these macromolecules undergo a regular self-folding process, during which double-stranded DNA (dsDNA) transitions into single-stranded DNA (ssDNA) at the kinked junctions. Our investigations, employing transmission electron microscopy (TEM), unprecedentedly reveal the absence of a PEG coating at these critical junctions, rendering them susceptible to nuclease degradation. This finding underscores the critical necessity for comprehensive PEG encapsulation in the engineering of robust gene delivery constructs. In stark contrast to the anisotropic rod-like condensates, our novel isotropic toroidal DNA condensates, characterized by comprehensive PEG shielding and a self-spooling mechanism that preserves dsDNA integrity, exhibit a marked enhancement in enzymatic stability (nearly 30-fold greater). Their favorable condensation process also confers superior transcriptional potential, positioning these toroidal condensates as promising platforms for the next generation of gene delivery systems.

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