He is most noted for his development of the concept of DNA nanotechnology beginning in the early 1980s. In fall 1980, while at a campus pub, Seeman was inspired by the M. C. Escher woodcut Depth to realize that a three-dimensional lattice could be constructed from DNA. He realized that this could be used to orient target molecules, simplifying their crystallographic study by eliminating the difficult process of obtaining pure crystals. In pursuit of this goal, Seeman's laboratory published the synthesis of the first three-dimensional nanoscale object, a cube made of DNA, in 1991. This work won the 1995 Feynman Prize in Nanotechnology. The concept of the dissimilar double DNA crossover introduced by Seeman, was important stepping stone towards the development of DNA origami.
Seeman, N (1982). "Nucleic acid junctions and lattices". Journal of Theoretical Biology. 99 (2): 237–47. 10.1016/0022-5193(82)90002-9. 6188926.—Considered to be the earliest paper outlining the concepts of DNA nanotechnology
Chen, Junghuei; Seeman, Nadrian C. (1991). "Synthesis from DNA of a molecule with the connectivity of a cube". Nature. 350 (6319): 631–3. 10.1038/350631a0. 2017259.—The synthesis of the DNA cube
Winfree, Erik; Liu, Furong; Wenzler, Lisa A.; Seeman, Nadrian C. (6 August 1998). "Design and self-assembly of two-dimensional DNA crystals". Nature. 394 (6693): 529–544. 10.1038/28998. 0028-0836. 9707114.—The synthesis of two-dimensional periodic lattices of double crossover molecules
Mao, Chengde; Sun, Weiqiong; Shen, Zhiyong; Seeman, Nadrian C. (14 January 1999). "A DNA Nanomechanical Device Based on the B-Z Transition". Nature. 397 (6715): 144–146. 10.1038/16437. 0028-0836. 9923675.—The first DNA-based nanomechanical device