In general, molecular design of RNA is difficult at the 3D level because of its highly complicated folding process. In the 1990s, biochemical and structural analyses revealed that many functional noncoding natural RNAs are organized into modules and fold into defined 3D structures. Moreover, several commonly used RNA–RNA binding motifs in these RNAs were identified by phylogenetic comparison and high-resolution structural analyses. Consequently, it has become possible to design self-folding RNAs precisely by employing such motifs and mimicking the modular organization of natural RNAs. As one such example, we have investigated the design and construction of a self-folding RNA scaffold consisting of standard doublestranded helices connected by the two RNA–RNA binding motifs. Results indicated that the constructed RNA folds compactly into the designed 3D structure. We have also reported the synthesis and development of an artificial RNA enzyme by installing a reaction site and a catalytic site into the designed RNA scaffold. For medical and biological applications, the goals of our current project are 1) to establish multifunctional RNP molecules with tumor seeking sensors, imaging agents and toxins that kill target cells, and 2) to establish artificial signal transduction systems for regulating function of a cell by employing designed RNA and RNP molecules. The strategy may be applicable to the synthesis and development of a variety of nonnatural functional RNAs with defined 3D structures.