C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
167/202, 195/1.1
C12N 15/00 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C07H 21/04 (2006.01) C12N 15/11 (2006.01) C12Q 1/68 (2006.01) C12Q 1/70 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2006008
METHOD FOR MAKING SYNTHETIC OLIGONUCLEOTIDES WHICH BIND SPECIFICALLY TO TARGET SITES ON DUPLEX DNA MOLECULES, BY FORMING A COLINEAR TRIPLEX, THE SYNTHETIC OLIGONUCLEOTIDES AND METHODS OF USE Abstract A method for making synthetic oligonucleotides which bind to target sequences in a duplex DNA forming colinear triplexes by binding to the major groove. The method includes scanning genomic duplex DNA and identifying nucleotide target sequences of greater than about 20 nucleotides having either about at least 65% purine bases or about at least 65% pyrimidine bases; and synthesizing synthetic oligonucleotides complementary to identified target sequences. The synthetic oligonucleotides have a G when the complementary location in the DNA duplex has a GC base pair and have a T when he complementary location in the DNA duplex has an AT base pair. The synthetic oligonucleotides are oriented 5' to 3' and bind parallel or 3' to 5' and bind anti-parallel to the about at least 65% purine strand. Also described are synthetic oligonucleotides made by the above methods. The oligonucleotides can be altered by modifying and/or changing the bases, adding linkers and modifying groups to the 5' and/or 3' termini, and changing the backbone. These synthetic oligonucleotides bind to duplex DNA to form triplexes. This process alters the functioning of the genes which are bound. This process can be used to inhibit cell growth, alter protein ratios, treat diseases including cancer and permanently alter the DNA. 5363G
Hogan Michael E.
Kessler Donald J.
Baylor College Of Medicine
Borden Ladner Gervais Llp
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