锁核酸和α-L-锁核酸：迈向治疗应用

LNA and alpha-L-LNA: towards therapeutic applications.

作者信息

Wengel Jesper, Vester Birte, Lundberg Lars Bo, Douthwaite Stephen, Sørensen Mads D, Babu B Ravindra, Gait Michael J, Arzumanov Andrey, Petersen Michael, Nielsen Jakob T

机构信息

Department of Chemistry, Nucleic Acid Center, University of Southern Denmark, Odense M, Denmark.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):601-4. doi: 10.1081/NCN-120021963.

DOI:10.1081/NCN-120021963

PMID:14565236

Abstract

LNA and alpha-L-LNA are promising candidates for the development of efficient oligonucleotide-based therapeutic agents. Here, we report dose-dependent inhibition of HIV-1 Tat-dependent trans activation by a 12-mer chimeric alpha-L-LNA/DNA oligomer. This oligomer exhibits a dose-dependency similar to that of the corresponding 12-mer chimeric LNA/2'-O-Me-RNA oligomer. In addition, we show that incorporation of alpha-L-LNA or LNA monomers into each of the two binding arms of a "10-23" DNAzyme markedly increases cleavage of the target RNA.

摘要

锁核酸（LNA）和α-L-锁核酸是开发高效寡核苷酸类治疗药物的有前景的候选物。在此，我们报道了一种12聚体嵌合α-L-锁核酸/DNA寡聚物对HIV-1反式激活因子Tat依赖性反式激活的剂量依赖性抑制作用。这种寡聚物表现出与相应的12聚体嵌合锁核酸/2'-O-甲基核糖核酸寡聚物相似的剂量依赖性。此外，我们表明，将α-L-锁核酸或锁核酸单体掺入“10-23”脱氧核酶的两个结合臂中，可显著增加对靶RNA的切割。