GENE-DIRECTED BIOLOGICALLY-ACTIVE SUBSTAN CES (ANTISENSE OLIGONUCLEOTIDES AND THEIR DERIVATIVES)

`Results of studies carried out over the last eight years under the Ru ssian State Scientific and Technical Program ''New Methods in Bioengin eering'' are reviewed. New addressing constructions formed by a tandem of two or more oligonucleotides on a target nucleic acid are describe d. The reactivity of the tandem is enhanced due to the stabilization o f some components, either by attachment of polyaromatic systems (metho d of effecters) 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 oligo nucleotides interact with the proteins of cells and living organisms, including the receptor proteins discovered in the course of this resea rch, the T-helper CD4 receptor, immunoglobulins, and some growth facto rs.