发明授权
US08658608B2 Modified triple-helix forming oligonucleotides for targeted mutagenesis
有权
用于靶向诱变的修饰的三螺旋形成寡核苷酸
- 专利标题: Modified triple-helix forming oligonucleotides for targeted mutagenesis
- 专利标题(中): 用于靶向诱变的修饰的三螺旋形成寡核苷酸
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申请号: US11562849申请日: 2006-11-22
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公开(公告)号: US08658608B2公开(公告)日: 2014-02-25
- 发明人: Peter M. Glazer , Michael M. Siedman
- 申请人: Peter M. Glazer , Michael M. Siedman
- 申请人地址: US CT New Haven US DC Washington
- 专利权人: Yale University,Department of Health and Human Services
- 当前专利权人: Yale University,Department of Health and Human Services
- 当前专利权人地址: US CT New Haven US DC Washington
- 代理机构: Pabst Patent Group LLP
- 主分类号: C12N15/11
- IPC分类号: C12N15/11 ; C07H21/04 ; C12N5/00
摘要:
High affinity, chemically modified triplex-forming oligonucleotides (TFOs) and methods for use thereof are disclosed. TFOs are defined as triplex-forming oligonucleotides which bind as third strands to duplex DNA in a sequence specific manner. Triplex-forming oligonucleotides may be comprised of any possible combination of nucleotides and modified nucleotides. Modified nucleotides may contain chemical modifications of the heterocyclic base, sugar moiety or phosphate moiety. A high affinity oligonucleotide (Kd≦2×10−8) which forms a triple strand with a specific DNA segment of a target gene DNA is generated. It is preferable that the Kd for the high affinity oligonucleotide is below 2×10−10. The nucleotide binds or hybridizes to a target sequence within a target gene or target region of a chromosome, forming a triplex region. The binding of the oligonucleotide to the target region stimulates mutations within or adjacent to the target region using cellular DNA synthesis, recombination, and repair mechanisms. The mutation generated activates, inactivates, or alters the activity and function of the target gene.