Advanced optical methods capable to diagnose sensitively biomolecular interactions in small quantities without the interaction site labeling, will be developed and applied to study of nucleic acid – protein interactions, in particular those playing important role in regulation of gene expression and/or in “antisense” therapy. Formation, structure and biochemical activity of enzyme – nucleic acid complexes in respect to the base sequence and/or nucleotide modification will be studied on selected cleavageand regulation enzymes. Methodological developments will comprise (i) technical and mathematical solution for precise Raman spectroscopy in nmol quantities, (ii) construction of high-resolution surface plasmon resonance sensor system with up to eight real-time observation channels, (iii) design of complex biomolecular interaction models considering effect of hydrodynamic conditions, (iv) preparation of structurally diverse sugar-phosphate backbone modified oligodeoxynucleotides.