发明名称 |
TRIPLEX-FORMING ANTISENSE OLIGONUCLEOTIDES HAVING ABASIC LINKERS TARGETING NUCLEIC ACIDS COMPRISING MIXED SEQUENCES OF PURINES AND PYRIMIDINES |
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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申请公布号 |
WO9640710(A1) |
申请公布日期 |
1996.12.19 |
申请号 |
WO1996US09093 |
申请日期 |
1996.06.05 |
申请人 |
HYBRIDON, INC.;KANDIMALLA, EKAMBAR;AGRAWAL, SUDHIR |
发明人 |
KANDIMALLA, EKAMBAR;AGRAWAL, SUDHIR |
分类号 |
A61K38/00;C07H21/00;C12N15/113;(IPC1-7):C07H21/00;A61K31/70 |
主分类号 |
A61K38/00 |
代理机构 |
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