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氯化-[4-(-三甲基铵基)苄基]壳聚糖作为基因载体:多聚体组成和细胞类型的影响。

-[4-(-Trimethylammonium)Benzyl]Chitosan Chloride as a Gene Carrier: The Influence of Polyplex Composition and Cell Type.

作者信息

Raik Sergei V, Mashel Tatiana V, Muslimov Albert R, Epifanovskaya Olga S, Trofimov Mikhail A, Poshina Daria N, Lepik Kirill V, Skorik Yury A

机构信息

Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi pr. VO 31, 199004 Saint Petersburg, Russia.

Department of Applied Optics, ITMO University, Kronverkskiy pr. 49, 197101 Saint Petersburg, Russia.

出版信息

Materials (Basel). 2021 May 10;14(9):2467. doi: 10.3390/ma14092467.

Abstract

Polyplex-based gene delivery systems are promising substitutes for viral vectors because of their high versatility and lack of disadvantages commonly encountered with viruses. In this work, we studied the DNA polyplexes with -[4-(-trimethylammonium)benzyl]chitosan chloride (TMAB-CS) of various compositions in different cell types. Investigations of the interaction of TMAB-CS with DNA by different physical methods revealed that the molecular weight and the degree of substitution do not dramatically influence the hydrodynamic properties of polyplexes. Highly substituted TMAB-CS samples had a high affinity for DNA. The transfection protocol was optimized in HEK293T cells and achieved the highest efficiency of 30-35%. TMAB-CS was dramatically less effective in nonadherent K562 cells (around 1% transfected cells), but it was more effective and less toxic than polyarginine.

摘要

基于多聚体的基因递送系统因其高度的通用性以及不存在病毒常见的缺点,而有望成为病毒载体的替代品。在这项工作中,我们研究了不同组成的-[4-(-三甲基铵)苄基]壳聚糖氯化物(TMAB-CS)与不同细胞类型中的DNA形成的多聚体。通过不同物理方法对TMAB-CS与DNA相互作用的研究表明,分子量和取代度对多聚体的流体动力学性质没有显著影响。高度取代的TMAB-CS样品对DNA具有高亲和力。转染方案在HEK293T细胞中得到优化,实现了30%-35%的最高效率。TMAB-CS在非贴壁K562细胞中的效果显著较差(约1%的转染细胞),但它比聚精氨酸更有效且毒性更小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/8126137/bb63b590ad67/materials-14-02467-g001.jpg

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