Beyond Watson-Crick: The Next 40 Years of Semantomorphic Science

Abstract

AbstractIt should come as no surprise that the world of DNA nanotechnology is still learning how to fully master the different steps of the self-assembly process. Semantomorphic science, as the late Ned Seeman would describe DNA nanotechnology, relies on the programmability of nucleic acids (semanto-) to encourage short oligomers to put themselves together (-morphic) into designed architectures (science?). In the same way that Gibson assembly frustrates the molecular biologist, semantomorphic self-assembly has for decades, and continues to, defy the scientist in question. In a brief analogy, Gibson assembly can be thought of as enzymatically directed self-assembly [1] that follows the same general rules as Seeman assembly: (1) guess conditions; (2) set up reaction; (3) pray to entity of choice; (4) check result; and (5) repeat as needed. In other words, when it works, it works well; when it doesn’t, troubleshooting the sticky-ended cohesion between too-large or too-small building blocks with imperfect assays can take months. Returning to semantomorphic science, it is still mesmerizing that any of this works at all, and for that, we owe our deepest gratitude to Ned and his generations-spanning vision.