Delivery of therapeutic oligonucleotides with cell penetrating peptides.
Delivery of therapeutic oligonucleotides with cell penetrating peptides.
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DOI：
10.1016/j.addr.2015.02.008
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发表时间：
2015-06-29
影响因子：
16.1
通讯作者：
Lebleu B
中科院分区：
文献类型：
--
作者：
Boisguérin P;Deshayes S;Gait MJ;O'Donovan L;Godfrey C;Betts CA;Wood MJ;Lebleu B
基于寡核苷酸的药物因其能够非常特异地调节基因表达而受到相当大的关注，因此它们已被应用于许多人类获得性或遗传性疾病的治疗。然而，临床翻译经常受到生物分布不佳的阻碍。细胞穿透肽(CPPs)似乎有可能增加核酸等非穿透性生物分子的细胞递送。本文综述了CPP介导的几类寡核苷酸，即反义寡核苷酸、剪接开关寡核苷酸和siRNAs。有两种主要的策略被用来运输带有CPP的ONS：共价共轭(更适合于类似物上的电荷中性)和非共价络合(基本上已经用于siRNA的输送)。将对化学合成、细胞内化的机制和各种应用进行综述。全面报道大量已公布的数据是不可能的。相反，重点放在已被证明在重要人类疾病的动物模型中有效的策略，以及从作者自己的专业知识中提取的例子。
Oligonucleotide-based drugs have received considerable attention for their capacity to modulate gene expression very specifically and as a consequence they have found applications in the treatment of many human acquired or genetic diseases. Clinical translation has been often hampered by poor biodistribution, however. Cell-penetrating peptides (CPPs) appear as a possibility to increase the cellular delivery of non-permeant biomolecules such as nucleic acids. This review focuses on CPP-delivery of several classes of oligonucleotides (ONs), namely antisense oligonucleotides, splice switching oligonucleotides (SSOs) and siRNAs. Two main strategies have been used to transport ONs with CPPs: covalent conjugation (which is more appropriate for charge-neutral ON analogues) and non-covalent complexation (which has been used for siRNA delivery essentially). Chemical synthesis, mechanisms of cellular internalization and various applications will be reviewed. A comprehensive coverage of the enormous amount of published data was not possible. Instead, emphasis has been put on strategies that have proven to be effective in animal models of important human diseases and on examples taken from the authors' own expertise.
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DOI：
10.1038/mtna.2012.30
发表时间：
2012-08-14
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.4
作者：
Crombez, Laurence;Aldrian-Herrada, Gudrun;Divita, Gilles
通讯作者：
Divita, Gilles
影响因子：
6.9
作者：
Christianson, Helena C.;Belting, Mattias
通讯作者：
Belting, Mattias
影响因子：
6.4
作者：
Boffa, L. C.;Cutrona, G.;Ferrarini, M.
通讯作者：
Ferrarini, M.
影响因子：
7.8
作者：
ALLINQUANT, B;HANTRAYE, P;PROCHIANTZ, A
通讯作者：
PROCHIANTZ, A