Nucleic Acid Structures

Abstract From the wide discipline of nucleic acid structure only selected topics have a direct bearing on antisense technology. Thus nucleic acid structure will not be discussed in this chapter as an independent field of research but as an essential factor for a particular field of application. The restrictions for selecting the topics of interest concern the structural elements as well as the solution conditions and the thermodynamic conditions. I shall mainly address RNA intramolecular structure and RNA:RNA double-strand formation. A few examples of DNA oligonucleotides directed against RNA targets will also be considered. Antisense technology is predominantly an in vivo technology, whereas studies on nucleic acid structure have been carried out in the past mainly in vitro. Therefore, in vitro conditions either have to be adapted to reflect the in vivo situation or the data have to be extrapolated. This requirement restricts the applicability of several experimental methods. Not only the solution conditions but also the thermodynamic approach has to resemble the requirements of antisense technology. Antisense RNA as well as target RNA act in structures which are formed right after synthesis in the cell. These structures, which might also exist as mixtures of conformers, deviate in many cases from the equilibrium structure. This complicates the experimental as well as the theoretical approach. Having these restrictions in mind, an outline will be given on the structures, on methods to predict them, and on experimental approaches for structure analysis.