Further development of DNA nanotechnology requires new functional oligonucleotides composed of nucleobases beyond the native four. In this review, we demonstrate new methodology for DNA and RNA functionalization using a base surrogate prepared from D-threoninol (2-amino-1,3-butanediol). Using this nucleobase surrogate, we can introduce functional molecules at any position of the sequence. Our methodology is conceptually similar to the copolymerization of multiple monomers: phosphoramidite monomers corresponding to the base surrogate and natural nucleotides are copolymerized on a solid support to prepare the functional oligonucleotides. Copolymerization allows for stable functional motifs, including wedges, interstrandwedges, dimers and clusters. By selecting suitable functional molecules and motifs, we can design photofunctional oligonucleotides, such as: (1) photoresponsive DNA that enables reversible formation and dissociation of the duplex by photoirradiation; (2) [2+ 2] photocycloaddition of stilbene derivatives; (3) orientation-dependent FRET (fluorescence (Forster) resonance energy transfer) systems; (4) sequence-specific fluorescent probe for the detection of DNA and RNA; and (5) functional siRNA for fluorescent labeling of mature RISC (RNA-induced silencing complex).