Toulmé J J, Tinévez R L, Brossalina E
INSERM U386, IFR Pathologies Infectieuses, Université Victor Segalen, Bordeaux II, France.
Biochimie. 1996;78(7):663-73. doi: 10.1016/s0300-9084(96)80012-5.
The presence of folded regions in RNA competes with the binding of a complementary oligonucleotide, resulting in a weak antisense effect. Due to the key role played by a number of RNA structures in the natural regulation of gene expression it might be of interest to design antisense sequences able to selectively interact with such motifs in order to interfere with the biological processes they mediate. Different possibilities have been explored. A high affinity oligomer will disrupt the structure; if the target structure is solved one can take advantage of unpaired bases (bulges, loops) to minimize the thermodynamic cost of the binding. Alternatively, the folded structure can be accommodated within the complex via the formation of a local triple helix. Oligomers able to adapt to the RNA structure (aptamers) can be extracted by in vitro selection from randomly synthesized libraries comprising several billions of sequences.
RNA中折叠区域的存在会与互补寡核苷酸的结合相互竞争，从而导致较弱的反义效应。由于许多RNA结构在基因表达的天然调控中发挥着关键作用，因此设计能够与这些基序选择性相互作用的反义序列以干扰它们介导的生物过程可能会很有意义。人们已经探索了不同的可能性。高亲和力的寡聚物会破坏结构；如果目标结构已解析，就可以利用未配对的碱基（凸起、环）来最小化结合的热力学成本。或者，折叠结构可以通过形成局部三螺旋而容纳在复合物中。能够适应RNA结构的寡聚物（适配体）可以通过体外筛选从包含数十亿个序列的随机合成文库中提取。
