Nucleic acid-based logic circuits
This invention relates to nucleic acid-based logic gates. The invention further relates to circuits comprising nucleic acid-based logic gates and methods of performing operations with the gates and circuits provided herein.
1. A logic gate complex comprising:
a) at least one output oligonucleotide comprising:
i) a first region comprising at least one toehold binding domain that forms a duplex with a complementary nucleic acid sequence of a gate oligonucleotide;
ii) a second region linked with the first region and comprising at least one single-stranded domain comprising an oligonucleotide that, upon release, functions as an input oligonucleotide sequence for a subsequent logic gate or as a signal sequence for detection of an operation, or a combination thereof;
iii) a third region linked with the second region and comprising a nucleic acid sequence that forms a duplex with a complementary nucleic acid sequence of a gate oligonucleotide;
b) at least one gate oligonucleotide comprising:
i) a first region comprising a single-stranded toehold binding domain complementary to an input oligonucleotide sequence;
ii) a second region comprising a nucleic acid sequence complementary to, and forming a duplex with, the first and third regions of the output oligonucleotide.
2. The logic gate of claim 1 , wherein the output or input oligonucleotide is 10 to about 200 nucleotides in length.
3. The logic gate of claim 1 , wherein the output or input oligonucleotide is 10 to about 100 nucleotides in length.
4. The logic gate of claim 1 , wherein the output or input oligonucleotide is 10 to about 50 nucleotides in length.
5. The logic gate of claim 1 , wherein the output oligonucleotide functions as an input oligonucleotide to a downstream gate.
6. The logic gate of claim 1 , wherein the output oligonucleotide and input oligonucleotide comprise RNA or DNA.
7. The logic gate of claim 1 , wherein the output oligonucleotide is detectably labeled.
8. The logic gate of claim 7 , wherein the detectable label is a fluorescent label.
9. The logic gate of claim 7 , wherein the detectable label comprises a material whose conductivity changes to indicate an output state.
10. The logic gate of claim 7 , wherein the detectable label comprises a material whose magnetization changes to indicate the output state.
11. The logic gate of claim 1 , wherein both the 5′ and 3′ ends of the output oligonucleotide are initially attached to the gate complex.
12. The logic gate of claim 1 , wherein the gate is a logical AND gate.
13. The logic gate of claim 1 , wherein the gate is a logical AND NOT gate.
14. The logic gate of claim 1 , wherein the gate is a logical NOT gate.
15. The logic gate of claim 1 , wherein the gate is a logical sensor gate, wherein an input is transduced into an output.
16. The logic gate of claim 1 , wherein the input oligonucleotide is an oligonucleotide associated with a disease marker.
17. A plurality of logic gates of claim 1 , wherein the output of one gate is the input of another gate.
18. The logic gate of claim 1 , wherein the input oligonucleotide or output oligonucleotide comprises a peptide nucleic acid.
19. A method of performing a logical operation comprising:
a) contacting the gate of claim 1 with a first input oligonucleotide that forms a duplex with a first toe-hold binding domain of a first gate oligonucleotide, wherein the first gate oligonucleotide is partially duplexed with a gate complex;
b) displacing the gate oligonucleotide from the gate complex by branch migration, thereby exposing a second toe-hold binding domain of a second gate oligonucleotide duplexed with an output oligonucleotide;
c) contacting the second toe-hold binding domain with a second input oligonucleotide;
d) displacing the second gate oligonucleotide from the gate complex by branch migration, thereby releasing the output oligonucleotide,
wherein release of the output oligonucleotide indicates that a logical operation has been performed.
20. The method of claim 19 , wherein the output oligonucleotide functions as an input nucleotide sequence for a subsequent logical operation or as a signal sequence for detection of an operation, or a combination thereof.
21. The method of claim 20 , wherein the output oligonucleotide is detectably labeled.
22. The method of claim 21 , wherein the detectable label is a fluorescent label.
23. The method of claim 21 , wherein the detectable label comprises a material whose conductivity changes to indicate an output state.
24. The method of claim 21 , wherein the detectable label comprises a material whose magnetization changes to indicate the output state.
25. The method of claim 19 , wherein the input oligonucleotide is an oligonucleotide associated with a disease marker.
26. The method of claim 19 , wherein the operation is detection of a disease marker.
27. The method of claim 19 , wherein the operation is transduction of an output oligonucleotide to at least one other gate.
28. The method of claim 27 , wherein the different gate is a logical AND gate.
29. The method of claim 27 , wherein the different gate is a logical AND NOT gate.
30. The method of claim 27 , wherein the different gate is a NOT gate.
31. The method of claim 27 , wherein the at least one other gate is a translator gate that can interconvert signals represented by different oligonucleotides.
32. The method of claim 27 , wherein the different gate is a repeater gate.
33. The method of claim 19 , wherein the gate is a logical sensor gate.
34. The method of claim 31 , wherein the translator gate provides an output oligonucleotide to a subcircuit.
35. A circuit comprising a plurality of logic gates of claim 1 .
36. The circuit of claim 35 , wherein the circuit is a Boolean circuit.
37. The circuit of claim 35 , wherein the circuit computes in multi-rail logic.