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修饰寡核苷酸的设计与应用

Design and applications of modified oligonucleotides.

作者信息

Gallo M, Montserrat J M, Iribarren A M

机构信息

Laboratorio de Química de Acidos Nucleicos, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET-UBA, Buenos Aires, Argentina.

出版信息

Braz J Med Biol Res. 2003 Feb;36(2):143-51. doi: 10.1590/s0100-879x2003000200001. Epub 2003 Jan 29.

Abstract

Oligonucleotides have a wide range of applications in fields such as biotechnology, molecular biology, diagnosis and therapy. However, the spectrum of uses can be broadened by introducing chemical modifications into their structures. The most prolific field in the search for new oligonucleotide analogs is the antisense strategy, where chemical modifications confer appropriate characteristics such as hybridization, resistance to nucleases, cellular uptake, selectivity and, basically, good pharmacokinetic and pharmacodynamic properties. Combinatorial technology is another research area where oligonucleotides and their analogs are extensively employed. Aptamers, new catalytic ribozymes and deoxyribozymes are RNA or DNA molecules individualized from a randomly synthesized library on the basis of a particular property. They are identified by repeated cycles of selection and amplification, using PCR technologies. Modified nucleotides can be introduced either during the amplification procedure or after selection.

摘要

寡核苷酸在生物技术、分子生物学、诊断和治疗等领域有广泛应用。然而,通过在其结构中引入化学修饰可以拓宽其用途范围。寻找新的寡核苷酸类似物的最活跃领域是反义策略,其中化学修饰赋予适当的特性,如杂交、抗核酸酶、细胞摄取、选择性,以及基本上良好的药代动力学和药效学性质。组合技术是另一个广泛应用寡核苷酸及其类似物的研究领域。适体、新的催化核酶和脱氧核酶是基于特定特性从随机合成文库中筛选出来的RNA或DNA分子。它们通过使用PCR技术的重复选择和扩增循环来鉴定。修饰的核苷酸可以在扩增过程中或选择后引入。

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