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首页> 外文期刊>Advanced Materials >Traceable Nano-Biohybrid Complexes by One-Step Synthesis as CRISPR-Chem Vectors for Neurodegenerative Diseases Synergistic Treatment
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Traceable Nano-Biohybrid Complexes by One-Step Synthesis as CRISPR-Chem Vectors for Neurodegenerative Diseases Synergistic Treatment

机译：通过一步合成的可追踪纳米生物冬小联复合物作为神经变性疾病协同治疗的CRISPR-CHEM载体

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摘要

Abnormal protein aggregations are essential pathological features of neurodegenerative diseases. Eliminating while inhibiting the regeneration of these protein aggregates is considered an effective treatment strategy. Herein, the CRISPR/Cas9 gene-editing tool is employed to inhibit the regeneration of disease-related proteins, while chemical drugs are applied to eliminate the proteins that are produced. To efficiently deliver CRISPR-chem drugs into brain lesions, traceable nano-biohybrid complexes (F-TBIO) are constructed by one-step synthesis and CRISPR/Cas9 plasmids (CF-TBIO) are loaded in a controllable manner. CF-TBIO can knock out the BACE1 gene and reduce the burden of amyloid-beta, and thereby significantly improve the cognitive abilities of 2xTg-AD mice. In particular, by prolonging the dosing interval, the pathological damage and behavioral abilities of 2xTg-AD mice are still significantly improved. During the therapeutic process, CF-TBIO with a high relaxation rate provides accurate imaging signals in the complex brain physiological environment. The finding shows that CF-TBIO has great potential to serve as a CRISPR-chem drug-delivery platform for neurodegenerative diseases therapy.
机译：异常蛋白质聚集是神经变性疾病的基本病理特征。在抑制这些蛋白质聚集体的再生的同时消除被认为是有效的治疗策略。这里，使用CRISPR / CAS9基因编辑工具来抑制疾病相关蛋白的再生，而化学药物被应用于消除产生的蛋白质。为了将CRISPR-CHEM药物有效地将CRISPR-CHEM药物分为脑病变，可追踪的纳米生物冬冬络合物（F-TBIO）由一步合成构成，并且以可控的方式装载CRISPR / CAS9质粒（CF-TBIO）。 CF-TBIO可以击出Bace1基因并减少淀粉样蛋白β的负担，从而显着提高2XTG-AD小鼠的认知能力。特别是，通过延长给药间隔，2XTG-AD小鼠的病理损伤和行为能力仍然显着改善。在治疗过程中，具有高松弛率的CF-TBIO在复杂的脑生理环境中提供精确的成像信号。该发现表明，CF-TBIO具有巨大的潜力，作为神经变性疾病治疗的CRISPR-CHEM药物输送平台。

著录项

  • 来源
    《Advanced Materials》 |2021年第27期|2101993.1-2101993.10|共10页
  • 作者

    Shen Jie; Lu Zhiguo; Wang Jianze; Hao Qiulian; Ji Weihong; Wu Yanyue; Peng Huan; Zhao Ruichen; Yang Jun; Li Yan; Shi Zhuyan; Zhang Xin;

  • 作者单位

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China|Univ Chinese Acad Sci Sch Chem Engn Beijing 100049 Peoples R China;

    Chinese Acad Sci Inst Proc Engn State Key Lab Biochem Engn Beijing 100190 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    CRISPR; Cas9; CRISPR-chem vectors; neurodegenerative diseases synergistic treatment; one-step synthesis; traceable nano-biohybrid complexes;

    机译：CRISPR;CAS9;CRISPR-CHEM载体;神经退行性疾病协同治疗;一步合成;可追踪的纳米生物冬冬复合物;

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