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Systems and methods for identifying miRNA targets and for altering miRNA and target expression

机译:鉴定miRNA靶标并改变miRNA和靶标表达的系统和方法

摘要

The present invention generally relates to microRNAs such as vertebrate microRNA (miRNA), for example, mammalian miRNA. Various aspects of the invention are directed to the detection, production, or expression of miRNA. In one aspect, the invention provides systems and methods for identifying targets of miRNA sequences. For instance, in one embodiment, gene sequences comprising UTRs are compared with miRNA sequences to determine the degree of interaction, for example, by determining a free energy measurement between the miRNA sequence and the UTR, and/or by determining complementarity between at least a portion of the miRNA sequence and the UTR. In another aspect, the invention is directed to the regulation of gene expression using miRNA. For example, gene expression within a cell may be altered by exposing the cell to an oligonucleotide comprising a sequence that is substantially antisense to at least a portion of an miRNA region of the gene, for example, antisense to a 6-mer or 7-mer portion of the miRNA. In still another aspect, the invention is directed to the treatment of cancer. For instance, in one set of embodiments, an isolated oligonucleotide comprising a sequence that is substantially antisense to an miRNA, or a portion of an miRNA, is administered to a subject having or being at risk of cancer. Yet other aspects of the invention are directed to compositions or kits including oligonucleotides comprising a sequence that is substantially antisense to an miRNA (or a portion of an miRNA), methods of promoting any of the above aspects, or the like.
机译:本发明一般涉及微小RNA,例如脊椎动物微小RNA(miRNA),例如哺乳动物miRNA。本发明的各个方面涉及miRNA的检测,产生或表达。一方面,本发明提供了用于鉴定miRNA序列靶标的系统和方法。例如,在一个实施方案中,将包含UTR的基因序列与miRNA序列进行比较,以确定相互作用的程度,例如,通过确定miRNA序列与UTR之间的自由能测量值,和/或通过确定至少一个RNA之间的互补性。 miRNA序列的一部分和UTR。在另一方面,本发明涉及使用miRNA调节基因表达。例如,可以通过将细胞暴露于包含基本上与该基因的miRNA区域的至少一部分反义的序列的寡核苷酸,例如与6-mer或7-反义的序列,来改变细胞内的基因表达。 miRNA的mer部分。在另一方面,本发明涉及癌症的治疗。例如,在一组实施方案中,将包含与miRNA或miRNA的一部分基本上反义的序列的分离的寡核苷酸施用于患有癌症或处于癌症风险中的受试者。本发明的其他方面涉及包含寡核苷酸的组合物或试剂盒,所述寡核苷酸包含与miRNA(或miRNA的一部分)基本上反义的序列,促进上述任何方面的方法等。

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