Problems in interpretation of data derived from in vitro and in vivo use of antisense oligodeoxynucleotides.

Problems in interpretation of data derived from in vitro and in vivo use of antisense oligodeoxynucleotides.
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反义寡脱氧核苷酸的体外和体内使用数据的解释问题。

DOI:
10.1089/ard.1994.4.67
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发表时间:
1994
期刊:
Antisense research and development
影响因子:
--
通讯作者:
Krieg,AM
Krieg,AM
中科院分区:
--
文献类型:
--
作者:
Stein,CA;Krieg,AM

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寡脱氧核苷酸以序列特异性方式抑制基因表达的能力已得到充分证实(综述见Stein和Cheng,1993)。由于其具有精确特异性的潜力,寡脱氧核苷酸(oligos)已被提议作为多种人类疾病的治疗剂,包括癌症、病毒感染和连接性组织病症。然而,长期以来已经认识到磷酸二酯(PO)寡聚物将不适合作为治疗剂,因为它们被核酸酶消化的速度快(Wickstrom,1986; Dagle等人,1991年)。这已经推动了具有修饰的主链的寡核苷酸的开发,例如核酸酶抗性硫代磷酸酯(PS)寡核苷酸,其现在容易合成并且通常使用(关于综述,参见Stein等人,1991年)。然而,在体外和体内使用PO、PS或其他带电寡核苷酸作为反义试剂存在几个关键问题,我们认为这些问题尚未得到充分解决。这篇社论试图定义这些问题,并就反义实验中获得的数据的解释提出本刊政策的声明。我们认为必须考虑几个关键点。
Theability of oligodeoxynucleotides to inhibit genetic ex¬ pression in a sequence-specific manner has been welldoc¬ umented (for a review, see Stein and Cheng, 1993). Because of their potential for exquisite specificity, oligodeoxynucleotides (oligos) have been proposed as therapeutic agents for a variety of human diseases, including cancer, viral infections, and con¬ nective tissue disorders. However, it has long been recognized that phosphodiester (PO) oligos will not be suitable as thera¬ peutic agents because of their rapid rate of digestion by nucle-ases (Wickstrom, 1986; Dagle et al., 1991). This has driven the development of oligos with modified backbones, such as the nuclease-resistant phosphorothioate (PS) oligos, which are now easily synthesized and in common use (for a review, see Stein et al., 1991). However, there are several crucial problems with the in vitro and in vivo use of PO, PS, or other charged oligos as antisense agents that we believe have not been sufficiently ad¬ dressed. This editorial seeks to define these problems, as well as to present a statement of the policy of this journal with re¬ spect to the interpretation of data obtained in antisense experi¬ ments. We believe that several critical points must be consid¬ ered.
淋巴细胞对寡脱氧核糖核苷酸的摄取是异质的且可诱导的。
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