Sprecher
Beschreibung
Living systems are an inspiring example of how fundamental functions can emerge from networks of interacting molecules. Competitive dimerization networks, for example, are composed by families of proteins that bind to each other to form a combinatorial library of dimers that play a crucial role in the downstream activation of specific signalling pathways. In recent years, synthetic DNA has emerged as an extraordinary nanomaterial to build synthetic molecular networks that exhibit complex input-output behaviour. Inspired by naturally-occurring systems, we demonstrate here a strategy to rationally program in-vitro transcription using synthetic DNA-based dimerization networks. The approach we propose is based on the use of a DNA-based competitive dimerization network consisting of DNA monomers modified with reactive groups that can covalently bond to each other and create a library of DNA dimer outputs. In the presence of specific DNA input strands that sequester DNA monomers, we can trigger the formation of a specific DNA dimer output able to activate an in-vitro transcription system. The strategy is highly versatile and we demonstrate the possibility to finely modulate the in-vitro transcription process using different network sizes and input sets. The programmability of these DNA-based dimerization networks also enables the orthogonal transcription of different fluorogenic aptamers. Finally, the DNA networks proposed here allow to perform complex input-output computations in a highly predictable and programmable manner.