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[溶瘤腺病毒在抗癌治疗中的现状与展望]

[Oncolytic adenoviruses in anti-cancer therapy: current status and perspectives].

作者信息

Sviatchenko V A, Tarasova M V, Netesov S V, Chumakov P M

出版信息

Mol Biol (Mosk). 2012 Jul-Aug;46(4):556-69.

Abstract

Lytic viral infection results in production of viral progeny, and lysis of the infected cells. Tumor cells are usually more sensitive to virus infection. Studies of viral oncolysis indicate that it could represent a promising alternative approach to cancer therapy. The ability of viruses to kill selectively cancer cells had been noticed for quite a long time ago. However, only in recent years, based on deeper understanding of molecular biology of viruses and the cell and due to the development of modern methods for directed modification of viruses, there emerged a real opportunity for development of virus variants with improved therapeutic potential. Adenoviruses represent one of the most studied models of oncolytic viruses. The DNA-containing viruses are very suitable for genetic manipulation and show minimal pathogenicity. The review summarizes data on directions and approaches aiming generation of highly efficient variants of oncolytic adenoviruses. The approaches include introduction of directed genetic modifications into viral genome, accelerated selection of oncolytic viral variants following treatment with mutagens, the use of adenoviruses as vectors for introduction of therapeutic gene products, optimization of viral delivery systems, minimalization of negative effects from the host immune system etc. The dynamic development of studies in the field holds promise for introduction into clinical practice of many variants of oncolytic adenoviruses in the very near future.

摘要

溶瘤病毒感染导致病毒子代的产生以及受感染细胞的裂解。肿瘤细胞通常对病毒感染更为敏感。病毒溶瘤研究表明,它可能是一种有前景的癌症治疗替代方法。病毒选择性杀死癌细胞的能力早在很久以前就已被注意到。然而,直到近年来,基于对病毒以及细胞分子生物学的更深入理解,并且由于现代病毒定向修饰方法的发展,才出现了开发具有更高治疗潜力病毒变体的真正机会。腺病毒是溶瘤病毒中研究最多的模型之一。含DNA病毒非常适合进行基因操作,并且致病性极低。这篇综述总结了旨在产生高效溶瘤腺病毒变体的方向和方法的数据。这些方法包括对病毒基因组进行定向基因改造、用诱变剂处理后加速溶瘤病毒变体的筛选、使用腺病毒作为引入治疗性基因产物的载体、优化病毒递送系统、将宿主免疫系统的负面影响最小化等。该领域研究的动态发展有望在不久的将来将许多溶瘤腺病毒变体引入临床实践。

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