A Solid-Support Methodology for the Construction of Geometrical Objects from DNA

A solid-support procedure has been developed for the synthesis of geometrical stick figures from branched DNA. The method permits control over the synthesis of individual edges of an object. Control derives from the restriction endonuclease digestion of hairpin loops forming each side of the new edge. Restriction sites are destroyed when the edge forms. Each cycle of the procedure creates an object that is covalently closed and topologically bonded to itself. This features permits destruction of incompletely ligated edges by exonuclease digestion, thereby purifying the growing object while it is still on the support. The use of the solid support permits convenient removal of reagents and catalysts from the growing product. The solid support also isolates individual objects from each other, thereby eliminating a class of potential side products. The strategy permits the separate execution of steps involving additions and cyclizations, which are optimized under different conditions. A technique is presented to rescue those hairpin loops that fail to be digested by restriction endonucleases. The synthesis of a quadrilateral from three-arm junctions utilizing this protocol is reported. In principle, the methodology can be used to combine more complex components, in order to fabricate polyhedra and two-dimensional or three-dimensional arrays.