[Gene-directed biologically active substances (antisense oligonucleotides and their derivatives)]

Results of studies carried out over the last eight years under the Russian State Scientific and Technical Program "New Methods in Bioengineering" are reviewed. New addressing constructions formed by a tandem of two or more oligonucleotides on a target nucleic acid are described. The reactivity of the tandem is enhanced due to the stabilization of some components, either by attachment of polyaromatic systems (method of effectors) or by the formation of a reaction center, which occurs when the components of the active center draw together into a tandem. Reagents which are oligonucleotide derivatives are also described, in particular a derivative of the antibiotic bleomycin, which is capable of catalytic cleavage of the target. Evidence is presented that oligonucleotides interact with the proteins of cells and living organisms, including the receptor proteins discovered in the course of this research, the T-helper CD4 receptor, immunoglobulins, and some growth factors.