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A microRNA complementary sequence is a specific nucleotide sequence designed to hybridize with a target microRNA (miRNA) via Watson-Crick base pairing. In pharmacology, these sequences are the primary components of antisense oligonucleotides (antimiRs) used to inhibit miRNAs that are upregulated in diseases such as cancer or viral infections (Lennox & Behlke, 2011). For instance, Miravirsen is an antisense drug that uses a sequence complementary to miR-122 to inhibit Hepatitis C virus replication (Janssen et al., 2013). Furthermore, these sequences are utilized in gene therapy as detargeting elements; by placing them in the 3' untranslated region of a transgene, expression is suppressed in tissues where the specific miRNA is present, thereby improving the safety profile of the therapy (Brown et al., 2006). While highly programmable, the use of these sequences faces hurdles such as efficient delivery to the cytoplasm and the potential for off-target binding to unintended RNA transcripts.
Antisense inhibition of microRNA function through competitive binding and sequestration.
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