Covalent Dynamic DNA Networks to Translate Multiple Inputs into Programmable Outputs

Area of Science:

• Synthetic biology
• Biochemistry
• Nanotechnology

Background:

• Naturally occurring protein dimerization networks exhibit complex input-output behaviors.
• Synthetic systems are needed to replicate and control such complex biological functions.

Purpose of the Study:

• To develop a fully synthetic DNA-based dimerization network for programmable input-output computations.
• To demonstrate control over DNA dimer output yields using specific DNA inputs.
• To showcase the versatility of the network using different covalent reactions and controlling DNA nanostructures.

Main Methods:

• Constructed DNA oligonucleotide monomers with reactive moieties for covalent bonding into dimers.
• Designed DNA input strands to sequester monomers, controlling network size and dimer yield.
• Employed thiol-disulfide and strain-promoted azide-alkyne cycloaddition (SPAAC) reactions for dimerization.
• Demonstrated control over functional dimer yields to regulate DNA nanostructure assembly and disassembly.

Main Results:

• Achieved programmable control over DNA dimer output yields through input strand sequestration.
• Successfully implemented dimerization networks using two distinct covalent chemistries.
• Showcased the ability to control the assembly and disassembly of DNA nanostructures via functional dimer outputs.
• Demonstrated that the DNA network can convert multiple inputs into predictable, controllable outputs.

Conclusions:

• The synthetic DNA dimerization network offers a programmable platform for complex computations, inspired by natural protein networks.
• This approach provides precise control over reaction yields and functional outputs, applicable to nanotechnology and synthetic biology.
• The covalent dynamic DNA networks represent a versatile tool for creating artificial systems with cell-like functions.