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TRIPLEX-FORMING ANTISENSE OLIGONUCLEOTIDES HAVING ABASIC LINKERS TARGETING NUCLEIC ACIDS COMPRISING MIXED SEQUENCES OF PURINES AND PYRIMIDINES
TRIPLEX-FORMING ANTISENSE OLIGONUCLEOTIDES HAVING ABASIC LINKERS TARGETING NUCLEIC ACIDS COMPRISING MIXED SEQUENCES OF PURINES AND PYRIMIDINES
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机译:具有碱性接头的三链体形成的反义寡核苷酸,具有靶向嘌呤和嘧啶的混合序列的核酸
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摘要
The present invention provides a novel class of antisense oligonucleotides capable of hybridizing to and inhibiting expression of nucleic acids having mixed purine/pyrimidine sequences by triplex formation. The foldback triplex-forming oligonucleotides (FTFOs) of the invention are comprised of three regions, a duplex-forming region, which is sufficiently complementary to a region of the target nucleic acid to hybridize to it under the conditions of interest, a triplex-forming region, which is an inverted repeat of the duplex-forming region and folds back upon the duplex formed between the duplex-forming region and the target nucleic acid to form a triplex, and a linker region, which connects the duplex-forming region and the triplex-forming region and allows formation of the triplex. A novel aspect of the FTFOs of the present invention is that from one to five abasic linkers substitute for nucleotides in the triplex-forming region and are positioned to match up with pyrimidine residues of the target when a triplex is formed. This allows the FTFOs of the present invention to target nucleic acid sequences having mixed purine/pyrimidine sequences. FTFOs according to the invention are useful for both in vitro and in vivo modulation of gene expression.
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