Processes for producing synthetic oligonucleotides that bind specifically to determination sites on duplex DNA molecules by forming a colinear triplex, the synthetic oligonucleotides and process for their production.

摘要

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 min to 3 min and bind parallel or 3 min to 5 min 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 min and/or 3 min 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.