Daisy Chain Topology Based Mammalian Synthetic Circuits for RNA-Only Delivery

ACS Synth Biol. 2020 Feb 21;9(2):269-282. doi: 10.1021/acssynbio.9b00313. Epub 2020 Jan 9.

Abstract

Owing to superior safety, the RNA-only delivery synthetic circuit is more suitable for cell-based medicine. Modules which possess matching inputs and outputs could be strung by daisy-chaining to compose RNA-only delivery synthetic gene circuits. In this study, we engineered well-characterized biological parts to construct composable modules, each of which could receive signals from the upstream module and transmit the processed signal to the next module using standard interfaces. Capsid-cNOT7, through which logic gates could be changed by merely changing the type of it, was used as the core element for logical process. Daisy chain topology was used to build RNA-only delivery mammalian synthetic circuits which possess validated functions such as fan out, protein sensing, drug sensing, light sensing, 2-input logic gate, 3-input logic gate, and volatile memory, providing a new method to simplify the design of RNA-only delivery synthetic circuits.

Keywords: RNA-binding protein; RNA-only delivery; post-transcriptional-regulation; protease; synthetic circuit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism
  • Cell Line
  • Cricetinae
  • Genes, Reporter
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Synthetic Biology / methods*
  • Transfection

Substances

  • 3' Untranslated Regions
  • Capsid Proteins
  • RNA, Messenger
  • Repressor Proteins
  • RNA