Methods for arbitrary peptide synthesis
View Patent ↗Methods, apparatus, systems, computer programs and computing devices related to biologically assembling and/or synthesizing peptides and/or proteins are disclosed.
1. A method comprising:
determining, with one or more computing units, an order that two or more types of charged tRNA are to be co-localized sequentially with one or more ribosome-based assemblers on or in a fluidic device; and
controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers.
2. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
synthesizing a target peptide by co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers.
3. The method of claim 1 , wherein two or more of the two or more types of charged tRNA have the same anti-codon and are optionally charged with different amino acids.
4. The method of claim 1 , wherein two or more of the two or more types of charged tRNA have one or more of different anti-codons or different tRNA and are charged with the same amino acid.
5. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing one or more first charged tRNA with the one or more ribosome-based assemblers;
co-localizing one or more second charged tRNA with the one or more ribosome-based assemblers; and
optionally repeating.
6. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more charged tRNA with the one or more ribosome-based assemblers at one or more first identifiable time intervals wherein the one or more first identifiable time intervals are at least partially based on one or more of a predicted rate of incorporation of two or more amino acids into one or more peptides, a predicted rate of activity of the one or more ribosome-based assemblers, a predicted rate of translocation of one or more nucleic acids, or a predicted rate of release of tRNA.
7. The method of claim 1 , further comprising:
monitoring one or more of amino acid incorporation into one or more peptides, ribosome-based assembler activity, nucleic acid translocation, or tRNA release.
8. The method of claim 7 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers at one or more first identifiable time intervals, and
wherein the one or more first identifiable time intervals are at least partially based on one or more of the amino acid incorporation into the one or more peptides, the ribosome-based assembler activity, the nucleic acid translocation, or the tRNA release.
9. The method of claim 7 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers at one or more first identifiable time intervals, and
wherein the one or more first identifiable time intervals are at least partially based on availability of one or more nucleic acid codons.
10. The method of claim 1 , further comprising:
monitoring one or more of presence or absence, concentration, or composition of one or more of the two or more types of charged tRNA or one or more tRNA.
11. The method of claim 10 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers at one or more first identifiable time intervals, and
wherein the one or more first identifiable time intervals are at least partially based on the concentrations of one or more of the two or more types of charged tRNA or the one or more tRNA.
12. The method of claim 10 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers at one or more first identifiable time intervals, and
wherein the one or more first identifiable time intervals are at least partially based on one or more of presence or absence of one or more of the two or more types charged tRNA or the one or more tRNA.
13. The method of claim 10 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers at one or more first identifiable time intervals, and
wherein the one or more first identifiable time intervals are at least partially based on one or more of presence or absence of one or more anti-codons on one or more of the two or more types of charged tRNA or the one or more tRNA.
14. The method of claim 1 , further comprising:
consuming sequentially the two or more types of charged tRNA.
15. The method of claim 1 , further comprising:
eliminating one or more of the two or more types of charged tRNA or one or more tRNA.
16. The method of claim 1 , further comprising:
removing one or more of the two or more types of charged tRNA or one or more tRNA.
17. The method of claim 16 , wherein removing one or more of the two or more types of charged tRNA or one or more tRNA comprises:
removing sequentially one or more of the two or more types of charged tRNA or the one or more tRNA.
18. The method of claim 16 , wherein removing one or more of the two or more types of charged tRNA or one or more tRNA comprises:
removing sequentially one or more of the two or more types of charged tRNA or the one or more tRNA at one or more second identifiable time intervals.
19. The method of claim 16 , further comprising:
monitoring one or more of presence or absence, concentration, or composition of one or more of the two or more types of charged tRNA or the one or more tRNA.
20. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
injecting sequentially the two or more types of charged tRNA into one or more receptacles containing the one or more ribosome-based assemblers.
21. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially two or more charged anti-stop codon tRNA with the one or more ribosome-based assemblers.
22. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers, wherein the two or more types of charged tRNA are charged with one or more natural amino acids, one or more unnatural amino acids, or one or more arbitrary amino acid.
23. The method of claim 1 , further comprising:
charging one or more tRNA with one or more natural amino acids, one or more arbitrary amino acid, or one or more unnatural amino acid.
24. The method of claim 1 , further comprising:
selecting the two or more types of charged tRNA.
25. The method of claim 24 , wherein selecting the two or more types of charged tRNA comprises:
selecting the two or more types of charged tRNA at least partially based on a target peptide sequence.
26. The method of claim 24 , wherein selecting the two or more types of charged tRNA comprises:
selecting the two or more types of charged tRNA at least partially based on a nucleic acid protein coding sequence.
27. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with one or more ribosome-based peptide assemblers.
28. The method of claim 1 , wherein co-localizing individually sequentially according to the determined order the two or more types of charged tRNA with one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with one or more prokaryotic ribosome-based assemblers.
29. The method of claim 1 , wherein co-localizing individually sequentially according to the determined order the two or more types of charged tRNA with one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with one or more eukaryotic ribosome-based assemblers.
30. The method of claim 1 , wherein co-localizing individually sequentially according to the determined order the two or more types of charged tRNA with one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with one or more mitochondrial ribosome-based assemblers.
31. The method of claim 1 , further comprising:
selecting the one or more ribosome-based assemblers.
32. The method of claim 1 , further comprising:
assembling one or more components of the one or more ribosome-based assemblers.
33. The method of claim 32 , wherein assembling one or more components of the one or more ribosome-based assemblers comprises:
assembling the one or more components of the one or more ribosome-based assemblers at one or more third identifiable time intervals.
34. The method of claim 32 , further comprising:
selecting the one or more components of the one or more ribosome-based assemblers.
35. The method of claim 1 , further comprising:
co-localizing the one or more ribosome-based assemblers at one or more identifiable locations.
36. The method of claim 34 , wherein co-localizing the one or more ribosome-based assemblers at one or more identifiable locations-comprises:
co-localizing the one or more ribosome-based assemblers at the one or more identifiable locations at one or more fourth identifiable time intervals.
37. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises co-localizing the two or more types of charged tRNA at least partially following co-localizing the one or more ribosome-based assemblers at one or more identifiable locations.
38. The method of claim 1 , further comprising:
affixing the one or more ribosome-based assemblers at one or more identifiable locations.
39. The method of claim 1 , further comprising:
affixing the one or more ribosome-based assemblers to one or more devices.
40. The method of claim 39 , wherein affixing the one or more ribosome-based assemblers to one or more devices comprises:
affixing the one or more ribosome-based assemblers to one or more MEMS devices.
41. The method of claim 1 , wherein controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers, wherein the one or more ribosome-based assemblers are co-localized with one or more nucleic acids.
42. The method of claim 41 , wherein co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers, wherein the one or more ribosome-based assemblers are co-localized with one or more nucleic acids comprises:
co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers, wherein the one or more ribosome-based assemblers are co-localized with the one or more nucleic acids having a selected protein coding sequence.
43. The method of claim 42 , further comprising:
synchronizing co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers, with the selected protein coding sequence of the one or more nucleic acids.
44. The method of claim 1 , further comprising:
co-localizing one or more nucleic acids with the one or more ribosome-based assemblers.
45. The method of claim 44 , wherein co-localizing one or more nucleic acids with the one or more ribosome-based assemblers comprises:
co-localizing the one or more nucleic acids with the one or more ribosome-based assemblers at one or more fifth identifiable time intervals.
46. The method of claim 44 , wherein the two or more types of charged tRNA are co-localized sequentially with the one or more ribosome-based assemblers at least partially following the one or more nucleic acids being co-localized with the one or more ribosome-based assemblers.
47. The method of claim 44 , further comprising:
selecting the one or more nucleic acids.
48. The method of claim 47 , wherein selecting the one or more nucleic acids comprises:
selecting the one or more nucleic acids having a target protein coding sequence.
49. The method of claim 48 , further comprising:
synchronizing co-localizing sequentially the two or more types of charged tRNA with the one or more ribosome-based assemblers, with the target protein coding sequence of the one or more nucleic acids.
50. A method of extra-cellular peptide synthesis comprising:
determining, with one or more computing units, an order that two or more charged tRNA are to be co-localized sequentially with one or more ribosome-based assemblers on or in a fluidic device; and
controlling the operation of the fluidic device with the one or more computing units so that the two or more charged tRNA are co-localized individually sequentially according to the determined order with the one or more ribosome-based assemblers in vitro.
51. A method comprising:
determining an assembly order, with one or more computing units, that two or more types of charged tRNA are to be co-localized with one or more ribosome-based assemblers on or in a fluidic device; and
controlling the operation of the fluidic device with the one or more computing units so that the two or more types of charged tRNA are co-localized individually sequentially according to the assembly order with the one or more ribosome-based assemblers based on the assembly order.
52. The method of claim 1 , further comprising:
receiving data representative of at least one of a target peptide structure or charged tRNA sequences; and
wherein determining, with one or more computing units, an order that two or more types of charged tRNA are to be co-localized sequentially with one or more ribosome-based assemblers on or in a fluidic device is based at least partially on the data.
53. The method of claim 50 , further comprising:
receiving data representative of at least one of a target peptide structure or charged tRNA sequences; and
wherein determining, with one or more computing units, an order that two or more charged tRNA are to be co-localized sequentially with one or more ribosome-based assemblers on or in a fluidic device is based at least partially on the data.
54. The method of claim 51 , further comprising:
receiving data representative of at least one of a target peptide structure or charged tRNA sequences; and
wherein determining an assembly order, with one or more computing units, that two or more types of charged tRNA are to be co-localized with one or more ribosome-based assemblers on or in a fluidic device is based at least partially on the data.