Reagents and methods

Abstract

A method of detecting a target nucleic acid sequence in a test solution comprising: A. providing a test solution comprising: a. RPA single-stranded DNA-binding protein (RPA-SSB) molecule; b. cleavage

Description

FIELD OF THE INVENTION The invention relates to new detection probes and detection methods which are suitable for use in a variety of detection applications, including for end-point and real-time monitoring of isothermal nucleic acid amplification reactions, particularly Recombinase Polymerase Amplification (RPA) reactions. BACKGROUND TO THE INVENTION Isothermal nucleic acid amplification methods are able to amplify target nucleic acids from trace levels to very high and detectable levels within a matter of minutes without the need for thermal cycling and associated instrumentation. Such isothermal methods include Recombinase Polymerase Amplification (RPA), as described in WO 2003 / 072805 and WO 2021 / 094746. WO 2021 / 094746 describes variant RPA methods referred to further herein as ‘mRPA’ which utilize reaction components tagged with intrinsically disordered regions. RPA methods can allow users to detect and quantify a particular sequence in trace amounts, facilitating point-of-care testing and increasing the accessibility and speed of diagnostics. Isothermal amplification methods can be monitored by end point detection (following amplification) or in real time (during amplification). The probes used for detection and quantification may differ depending on application strategy. SUMMARY OF THE INVENTION The present invention relates to new detection methods and reagents which may find utility in a variety of detection applications, including for end-point and real-time monitoring of isothermal nucleic acid amplification reactions, particularly Recombinase Polymerase Amplification (RPA) reactions. A summary of aspects of the invention is provided below. Aspects of the Invention 1. A method of detecting a target nucleic acid sequence of interest in a test solution, the method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (RPA-SSB) molecule; b. a cleavage molecule; c. a detection probe according to any one of aspects 61 to 108; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. 2. A method according to aspect 1, wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. 3. A method according to aspect 2, wherein after the providing step (A), the method further comprises performing a RPA reaction comprising one or more cycles of amplification, and detecting the detectible signal during the one or more cycles of amplification in real time, or at the end of the one or more cycles of amplification. 4. A method according to any one of aspects 1 to 3, wherein the RPA-SSB is selected from the group consisting of Gp32, E. coll SSB protein, phage T4 Gp32 protein, phage Rb69 Gp32, phage vB^EcoM^NBGl Gp32, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably the RPA-SSB is Gp32 or phage vBEcoMNBGl Gp32. 5. A method according to aspect 4, wherein the RPA-SSB is tagged with one or more functional intrinsically disordered regions (IDRs), preferably as a genetically engineered fusion protein comprising the RPA-SSB and an amino acid sequence comprising or consisting of the one or more functional IDRs. 6. A method according to any one of aspects 2 to 5, wherein the recombinase agent is selected from the group consisting of UvsX, T4 UvsX, T6 UvsX, RBI8 UvsX, E.coli phage wV7 UvsX, Shigella phage CB8 UvsX, Shigella phage Shfl2 UvsX, E.coli phage ARI UvsX, phage vB_EcoM_G4507 UvsX, Shigella phage SHFML-11 UvsX, Escherichia phage vB EcoM DalCa UvsX, E. coli RecA, E. coli RadA, E. coli RadB, E. coli Rad 51 or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the recombinase agent is UvsX, more preferably Escherichia phage vBEcoMDalCa UvsX. 7. A method according to any one of aspects 2 to 6, wherein the recombinase loading protein is selected from the group consisting of UvsY, E. coli RecO, E. coli RecR or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the recombinase loading protein is UvsY, more preferably Escherichia phage STO UvsY. 8. A method according to any one of aspects 2 to 7, wherein the polymerase is: A. a eukaryotic polymerase selected from the group consisting of pol-u, pol-P, pol-5, pol-E or any functional analog, homolog or derivative thereof, and any combination thereof; B. a prokaryotic polymerase selected from the group consisting of Bacillus stearothermophilus polymerase I large fragment, Bacillus subtilis Pol I large fragment (Bsu polymerase), Listeria monocytogenes DNA polymerase I, S. aureus DNA polymerase I (Sau polymerase), E. coli DNA polymerase I Klenow fragment, E. coli DNA polymerase I, E. coli DNA polymerase II, E. coli DNA polymerase III, E. coli DNA polymerase IV, E. coli DNA polymerase V, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the polymerase is S. aureus DNA polymerase I (Sau polymerase) or Bacillus subtilis Pol I large fragment (Bsu polymerase); C. a bacteriophage polymerase selected from the group consisting of bacteriophage T4 gp43 DNA polymerase, T7 DNA polymerase and Phi-29 DNA polymerase, or any functional analog, homolog or derivative thereof, and any combination thereof. 9. A method according to any one of aspects 1 to 8, wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; wherein the cleavage molecule is Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. 10. A method according to any one of aspects 1 to 9, wherein the signal-promoting molecule is: A. a quencher; B. a fluorophore; C. a polypeptide, preferably which: a. has enzymatic activity; b. is a component of an enzyme complex, is a domain of an enzyme, is a fragment of an enzyme or is an enzyme cofactor; or c. is an activator of an enzyme or an enzyme complex; D. a small molecule, preferably which: a. promotes the formation of a molecular complex, such as a protein:protein complex; b. promotes the activation of an enzyme or an enzyme complex; or c. is a cofactor of an enzyme or an enzyme complex. 11. A method according to aspect 10(A), wherein the probe is a probe according to any one of aspects 78 to 80, 83, 84, 85, 86(1) and 86(2), and wherein the step of detecting the detectable signal comprises detecting fluorescence emission produced by the fluorophore of the probe. 12. A method according to aspect 10(B), wherein the probe is a probe according to any one of aspects 80 to 85, 86(3) and 86(4), and wherein the step of detecting the detectable signal comprises detecting fluorescence emission produced by the fluorophore of the probe. 13. A method according to aspect 11 or aspect 12, wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQIDNO: 1. 14. A method according to any one of aspects 1 to 9, wherein the signal-promoting molecule is a polypeptide, wherein the probe is a probe according to aspect 87, and wherein the detectible signal is produced in a reaction which is dependent upon the polypeptide of the probe. 15. A method according to aspect 10(C)(a), wherein the probe is a probe according to aspect 88, and wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the polypeptide of the probe. 16. A method according to aspect 15, wherein the probe is a probe according to aspect 89 or 90, and wherein the detectible signal is produced in a reaction in a solution which is dependent upon the enzymatic activity of HRP of the probe, the method comprising detecting the activity of the HRP enzyme (HRP holoenzyme) in the solution. 17. A method according to aspect 16, wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), optionally wherein TDP-1 has the amino acid sequence as set forth in SEQ ID NO: 3 or SEQ ID NO: 4. 18. A method according to aspect 10(C)(b), wherein the probe is a probe according to aspect 91, and wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the enzyme or enzyme complex comprising the component, the enzymatic activity of the enzyme comprising the domain, the enzymatic activity of the enzyme comprising the fragment, the enzymatic activity of the enzyme comprising the cofactor. 19. A method according to aspect 18, wherein the probe is a probe according to aspect 92 or 93, and wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of beta-galactosidase mediated by the beta-galactosidase alpha peptide of the probe. 20. A method according to aspect 19, wherein the cleavage molecule is Escherichia coh Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1. 21. A method according to any one of aspects 18 to 20, wherein the step of detecting the detectible signal comprises: 1) contacting the beta-galactosidase alpha peptide of the probe in solution with betagalactosidase omega fragment (omega peptide) to form beta-galactosidase holoenzyme; and 2) detecting the presence of beta-galactosidase holoenzyme in solution. 22. A method according to aspect 10(C)(c), wherein the probe is a probe according to aspect 34, and wherein the detectible signal is produced in a reaction which is dependent upon activation of the enzyme or enzyme complex by the polypeptide of the probe. 23. A method according to aspect 22, wherein the probe is a probe according to aspect 95 or 96, and wherein the detectible signal is produced in a reaction which is dependent upon activation of the enzyme or enzyme complex by the M13 polypeptide of the probe. 24. A method according to aspect 23, wherein the detectible signal is produced in a reaction which is dependent upon activation an enzyme by the Ml 3 polypeptide of the probe, wherein the enzyme is SUMO 1 / sentrin specific peptidase 1 (SENP1). 25. A method according to aspect 72, wherein the detectible signal is produced in a reaction comprising: A. contacting the M13 polypeptide of the probe with SUMOl / sentrin specific peptidase 1 (SENP1) in the presence of a SUMO-alpha peptide fusion protein, whereupon SENP1 catalyses the cleavage of the SUMO-alpha peptide fusion protein to release free beta-galactosidase alpha peptide, and B. detecting the presence of free beta-galactosidase alpha peptide. 26. A method according to aspect 25, wherein the step detecting the presence of free alpha peptide comprises: 1) contacting the beta-galactosidase alpha peptide of the probe in solution with betagalactosidase omega fragment (omega peptide) to form beta-galactosidase holoenzyme; and 2) detecting the presence of beta-galactosidase holoenzyme in solution. 27. A method according to aspect 21 or aspect 26, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: a colorimetric assay, a fluorescence assay, a chemiluminescence assay, a bioluminescence assay or an electrochemical assay. 28. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with orthonitrophenyl-P-D-galactopyranoside (ONPG) in solution, thereby forming a chromophore reaction product ortho-nitrophenol (ONP), and B. detecting the presence of ortho-nitrophenol (ONP), optionally by measuring the absorbance of the solution at 420 nm. 29. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with chlorophenol red-P-D-galactopyranoside (CPRG) in solution, thereby forming a chromophore reaction product chlorophenol red; and B. detecting the presence of chlorophenol red, optionally by measuring the absorbance of the solution at 570 to 595 nm, e.g. 575 nm. 30. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-bromo-4-chloro-3-indolyl-P-D-galactopyranoside in solution, thereby forming a blue precipitate reaction product 5,5'-dibromo-4,4'-dichloro-indigo; and B. detecting the presence of 5,5'-dibromo-4,4'-dichloro-indigo. 31. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-Bromo-3-indolyl P-D-galactopyranoside in solution, thereby forming a blue precipitate reaction product 5,5'-dibromo-indigo; and B. detecting the presence of 5,5'-dibromo-indigo. 32. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-Bromo-6-chl oro-3-indolyl-P-D-galactopyranoside in solution, thereby forming a magenta precipitate reaction product 5,5' dibromo-6,6'-dichloro-indigo; and B. detecting the presence of 5,5' dibromo-6,6'-dichloro-indigo, optionally by measuring the absorbance of the solution at 565 nm. 33. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 6-Chloro-3-indolyl-beta-D-galactopyranoside in solution, optionally together with nitroblue tetrazolium salt (NBT), thereby forming a precipitate reaction product 6,6' dichloro indigo; and B. detecting the presence of 6,6' dichloro indigo. 34. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 3,4-Cyclohexenoesculetin p-D-galactopyranoside in the presence of Fe3+ in solution, thereby forming a black precipitate reaction product, which is a complex formed of 2 molecules of 3,4-Cyclohexenoesculetin (2,3-dihydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one) and one Fe3+; and B. detecting the presence of the black precipitate reaction product. 35. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-Iodo-3-indolyl-P-D-galactopyranoside in solution, thereby forming a purple precipitate reaction product 5,5'-diiodo indigo; and B. detecting the presence of 5,5'-diiodo indigo, optionally by immunoblotting, or by measuring the absorbance of the solution at 575 nm. 36. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with l-Methyl-3-indolyl-P-D-galactopyranoside in solution, thereby forming a green precipitate reaction product l,l'-dimethyl isoindigo; and B. detecting the presence of 1,l'-dimethyl isoindigo. 37. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 6-O-P-galactopyranosyl-luciferin in solution in the presence of luciferase, preferably firefly luciferase; and B. detecting the emission of light (luminescence), preferably by measuring emission at 560 nm. 38. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 3-chloro-5-5-chloro-4-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenoxy-beta-galactopyranoside (Galacton Star) or 2-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenoxy-beta-galactopyranoside (Galacton plus) in solution; and B. detecting the production of 3-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenolate or 2-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenolate moiety by detecting chemiluminescence. 39. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 7-(P-D-galactopyranosyloxy)-3h-phenoxazin-3-one (resorufin P-D-galactopyranoside) in solution, thereby releasing 7-hydroxy-3H-phenoxazin-3-one (resorufin); and B. detecting the presence of resorufin, optionally by measuring the fluorescence emission of the solution at 580 nm upon excitation at 570 nm. 40. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-Methylumbelliferyl-P-D-galactopyranoside (4-Methylumbelliferyl-P-D-galactoside; MUG) in solution, thereby releasing 4-methylumbelliferone (4-MU); and B. detecting the presence of 4-MU, optionally by measuring the fluorescence emission of the solution at 445 nm upon excitation at 372 nm. 41. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with fluorescein di(P-D-galactopyranoside) (FDG) in solution, thereby releasing fluorescein; and B. detecting the presence of fluorescein, optionally by measuring the fluorescence emission of the solution at 517-519 nm upon excitation at 495-498 nm. 42. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-amynophenyl-beta-D-galactopyranoside (ANPG) to form 4-aminophenol; B. oxidising 4-aminophenol at an electrode, the electrode comprising or consisting of a conductive material, such as carbon, graphite, graphene, gold, platinum, or conductive metal oxides, and measuring the current through the electrode; and C. detecting a change in the current, whereby an increase in the current correlates with an increase in the rate of formation of 4-aminophenol. 43. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-Methoxyphenyl-P-d-galactopyranoside (MPGP) to produce 4-methoxyphenol; B. detecting 4-methoxyphenol at an electrode by an electrochemical detection method, optionally by voltammetry or by amperometry, the electrode comprising or consisting of a conductive material, such as carbon, graphite, graphene, gold, platinum, or conductive metal oxides, and measuring the current through the electrode; and C. detecting a change in the voltage or current, whereby an increase in the voltage or current correlates with an increase in the rate of formation of 4-methoxyphenol. 44. A method according to aspect 27, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-Methoxyphenyl-P-d-galactopyranoside (MPGP) in the presence of an oxidase, preferably tyrosinase, to form 4-methoxycatechol; B. detecting 4-methoxycatechol at an electrode by an electrochemical detection method, optionally by voltammetry or by amperometry, by oxidising 4-methoxycatechol at an electrode, the electrode comprising or consisting of a conductive material, such as carbon, graphite, graphene, gold, platinum, or conductive metal oxides, and measuring the current through the electrode; and C. detecting a change in the voltage or current, whereby an increase in the voltage or current correlates with an increase in the rate of oxidation of 4-methoxycatechol. 45. A method according to any one of aspects 1 to 9, wherein the signal-promoting molecule is a small molecule, wherein the probe is a probe according to aspect 97, and wherein the detectible signal is produced in a reaction which is dependent upon the small molecule of the probe. 46. A method according to aspect 10(D)(a), wherein the probe is a probe according to aspect 98, and wherein the detectible signal is produced in a reaction which is dependent upon the formation of a molecular complex, such as a protein:protein complex, mediated by the small molecule of the probe. 47. A method according to aspect 46, wherein: A. the probe is a probe according to aspect 99 or 100, and wherein the detectible signal is produced in a reaction which is dependent upon the formation of a protein:protein complex mediated by the everolimus small molecule of the probe; or B. the probe is a probe according to aspect 101 or 102, and wherein the detectible signal is produced in a reaction which is dependent upon the formation of a protein:protein complex mediated by the rapamycin small molecule of the probe. 48. A method according to aspect 47, wherein the step of detecting the detectible signal comprises: A. contacting the everolimus or rapamycin of the probe with FK506 binding protein (FKBP) and FKBP-rapamycin-binding (FRB) domain in solution, whereby everolimus or rapamycin causes the dimerization of FKBP and FBR, and B. detecting the presence of the FKBP-FBR dimer in the solution. 49. A method according to aspect 48, wherein the step of detecting the presence of the FKBP-FBR dimer comprises: A. providing a circular-permutated nano-luc fusion protein comprising (in sequential order in the direction N-terminal to C-terminal): i. FKBP, preferably having the amino acid sequence GVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPF KFMLGKQEVIRGWEEGV AQMS V GQRAKLTISPD Y AY GAT GHPGIIP PHATLVFDVELLKLE (SEQ ID NO: 52); and ii. a first linker, preferably having the amino acid sequence GGSGGSGG (SEQ ID NO: 53); and iii. a C-terminal portion of nano-luc, preferably having the amino acid sequence VTGWRLCERILA (SEQ ID NO: 54); and iv. a second linker, preferably having the amino acid sequence GGSGSGSGSGGSGSGGS (SEQ ID NO: 55); and v. the remaining (N-terminal) portion of nano-luc, preferably having the amino acid sequence DNMVFTLEDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPI QRIVLSGENGLKIDIHVIIPYEGLSGDQMGQIEKIFKVVYPVDDHHFK VILHYGTLVIDGVTPNMIDYFGRPYEGIAVFDGKKITVTGTLWNGN KIIDERLINPDGSLLFRVTING (SEQ ID NO: 56); and vi. a third linker, preferably having the amino acid sequence SGSGSGG (SEQ ID NO: 57); and vii. FBR, preferably having the amino acid sequence LWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTL KETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVF RRIS (SEQ ID NO: 58); optionally wherein the fusion protein has an affinity tag at the N-terminal end of the protein before the FKBP sequence, preferably a six-histidine tag immediately before the FKBP sequence; and wherein nano-luc is the ATP independent 19.1 kDa catalytically-active subunit of the luciferase enzyme of Oplophorus gracilirostris\ B. contacting the everolimus or rapamycin of the probe with the fusion protein in the presence of 2-furanylmethyl-deoxy-coelenterazine (furimazine) or 6-(4- Hydroxyphenyl)-2-[(4-hydroxyphenyl)methyl]-8-(phenylmethyl)-7H-imidazo[l,2-a]pyrazin-3-one (coelenterazine); and C. detecting the emission of light (luminescence), optionally by measuring emission at 460 nm. 50. A method according to aspect 10(D)(b), wherein the probe is a probe according to aspect 103, and wherein the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex mediated by the small molecule of the probe. 51. A method according to aspect 50, wherein the probe is a probe according to aspect 104 or 105, and wherein the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex mediated by the methotrexate small molecule of the probe. 52. A method according to aspect 51, wherein the step of detecting the detectible signal comprises: A. contacting the methotrexate (MTX) of the probe with a binding partner to form a protein binding partner:MTX complex; and B. detecting the presence of the complex. 53. A method according to aspect 52, wherein the step of detecting the detectible signal comprises: A. contacting the MTX of the probe with a fusion protein comprising glucose dehydrogenase (GDH) and a calmodulin domain (CaM-GDH) together with the protein binding partner (CaM-GDH-protein binding partner); and B. measuring GDH activity. 54. A method according to aspect 53, wherein: A. the methotrexate:protein binding partner complex comprises a dihydrofolate reductase:MTX complex and the step detecting the complex comprises contacting the cleaved MTX with a CaM-GDH-dihydrofolate reductase fusion protein, and measuring GDH activity; B. the methotrexate:protein binding partner complex comprises a thymidylate synthase:MTX complex and the step detecting the complex comprises contacting the cleaved MTX with a CaM-GDH-thymidylate synthase fusion protein, and measuring GDH activity; or C. the methotrexate :protein binding partner complex comprises an anti-methotrexate VHH antibody:MTX complex and the step detecting the complex comprises contacting the cleaved MTX with a CaM-GDH-anti-methotrexate VHH antibody fusion protein, and measuring GDH activity. 55. A method according to aspect 54, wherein GDH activity is measured via a colorimetric assay or via an electrochemical assay. 56. A method according to aspect 10(D)(c), wherein the probe is a probe according to aspect 106, and wherein the detectible signal is produced in a reaction which is dependent upon the conversion of an apoenzyme or apoenzyme complex into a holoenzyme or holoenzyme complex mediated by the small molecule cofactor of the probe. 57. A method according to aspect 56, wherein the probe is a probe according to aspect 107 or 108, and wherein the detectible signal is produced in a reaction which is dependent upon the conversion of an apoenzyme or apoenzyme complex into a holoenzyme or holoenzyme complex mediated by the hemin small molecule of the probe. 58. A method according to aspect 57, wherein the detectible signal is produced in a method comprising: A. contacting in a solution the hemin of the probe with horseradish peroxidase (HRP) apoenzyme, thereby forming HRP holoenzyme; and B. detecting the activity of HRP holoenzyme in the solution. 59. A method according to aspect 58, wherein the step of detecting the activity of HRP holoenzyme in the solution comprises reacting HRP holoenzyme in the solution with an oxidase and a substrate for the oxidase, and detecting the presence of a product produced by the reaction. 60. A method according to aspect 16, aspect 17, aspect 58, or aspect 59, wherein the step of detecting the activity of HRP holoenzyme in the solution comprises: A. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase, p-hydroxybenzoic acid and 4-aminoantipyrine; or b) p-hydroxybenzoic acid, 4-aminoantipyrine and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 504 nm; or B. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase and 3,3',5,5'-tetramethybenzidine (TMB); or b) 3,3',5,5'-tetramethybenzidine (TMB) and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 450 nm or 650 nm; or C. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase and 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS); or b) 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 405 nm. 61. A detection probe for detecting a target nucleic acid sequence of interest in a test solution, the test solution comprising a recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB), a cleavage molecule and a target nucleic acid sequence of interest; wherein the probe comprises: A. one or two single-stranded oligonucleotides each comprising a sequence which is complementary to a target nucleic acid sequence of interest; and B. a repressible cleavage-dependent signalling system which: a. comprises a signal-promoting molecule tethered to the oligonucleotide(s) via at least one linker, wherein the at least one linker is attached to the signal-promoting molecule and to a chemical group of the oligonucleotide(s) and thereby defines a cleavage site on the oligonucleotide(s); b. provides a detectible signal which: l.is dependent upon cleavage at the cleavage site by the cleavage molecule, and 2.following hybridisation of the oligonucleotide(s) with the target sequence, is not dependent upon: 1. cleavage of the oligonucleotide(s) at an apurinic / apyrimidinic site (abasic site) of the oligonucleotide(s), e.g. at a 3'-side of an abasic site and / or at a 5'-side of the abasic site, or at a site comprising an abasic furan; or 2. cleavage of the oligonucleotide(s) at a mismatch site; and c. is configured so that when the probe is present in the test solution: l.when the oligonucleotide(s) is not hybridised with the target sequence, cleavage at the cleavage site by the cleavage molecule is inhibited and production of a detectible signal is thereby repressed; and 2.upon hybridisation of the oligonucleotide(s) with the target sequence, the cleavage molecule cleaves at the cleavage site, thereby producing a detectible signal. 62. A detection probe according to aspect 61, wherein the linker(s): A. is not attached to an abasic nucleotide or an abasic residue of the oligonucleotide(s), e.g. the sugar molecule of an abasic nucleotide; and / or B. is not attached to the oligonucleotide(s) at a nucleotide or residue position adjacent to a position in the oligonucleotide which is occupied by an abasic nucleotide or an abasic residue. 63. A detection probe according to aspect 61 or aspect 62, wherein each of the one or two oligonucleotides is about 20 to 70 nucleotide positions in length, preferably between about 30 to 60 nucleotide positions in length. 64. A detection probe according to any one of aspects 61 to 63, further comprising a polymerase extension blocking group attached to the 3’ end of the oligonucleotide(s), optionally wherein the blocking group is a spacer, such as a C3-spacer. 65. A detection probe according to any one of aspects 61 to 64, wherein: i. the target nucleic acid sequence of interest is DNA and the detection probe is a detection probe for detecting a target DNA sequence of interest; or ii. the target nucleic acid sequence of interest is RNA and the detection probe is a detection probe for detecting a target RNA sequence of interest. 66. A detection probe according to any one of aspects 61 to 65, wherein when present in the test solution the recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB) is selected from the group consisting of Gp32, E. coli SSB protein, phage T4 Gp32 protein, phage Rb69 Gp32, phage vBEcoMNBGl Gp32, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably the RPA-SSB is Gp32 or phage vB^EcoMJNBGl Gp32. 67. A detection probe according to aspect 66, wherein the RPA-SSB is tagged with one or more functional intrinsically disordered regions (IDRs), preferably as a genetically engineered fusion protein comprising the RPA-SSB and an amino acid sequence comprising or consisting of the one or more functional IDRs. 68. A detection probe according to any one of aspects 61 to 67, wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; wherein the cleavage molecule is Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. 69. A detection probe according to any one of aspects 61 to 68, wherein in each one of the one or two oligonucleotides the signal-promoting molecule is tethered to the oligonucleotide(s) by a linker which is attached to the signal-promoting molecule and to a chemical group of the terminal nucleotide at the 3’ end of the oligonucleotide(s), preferably to the 3’ terminal phosphate group of the oligonucleotide(s), and wherein: A. the chemical group to which the linker is attached, preferably the 3’ terminal phosphate group, comprises the cleavage site; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal. 70. A detection probe according to any one of aspects 61 to 68, wherein in each one of the one or two oligonucleotides the signal-promoting molecule is tethered to the oligonucleotide(s) by two linkers, wherein: (i) a first linker is attached to a first position on the signal-promoting molecule and to a chemical group at nucleotide position n in the oligonucleotide(s), and (ii) a second linker is attached to a second position on the signalpromoting molecule and to a chemical group at nucleotide position n+x in the oligonucleotide(s) wherein: A. the chemical group on the oligonucleotide(s) to which the first linker is attached comprises the cleavage site, preferably the 3’ terminal phosphate group; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal; and wherein the terminal nucleotide position at the 3’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 5’ end of the oligonucleotide(s) are defined as n+x, wherein x is an integer of 0 or more. 71. A detection probe according to aspect 70, wherein the chemical group of the oligonucleotide(s) to which the first linker is attached is the 3’ terminal phosphate group at position n of the oligonucleotide(s). 72. A detection probe according to aspect 71, wherein: A. the second linker is attached to a chemical group at nucleotide position n in the oligonucleotide(s); or B. the second linker is attached to a chemical group at nucleotide position n+1 in the oligonucleotide(s); or C. the second linker is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), wherein x is an integer of 2 or more. 73. A detection probe according to aspect 70, wherein the chemical group of the oligonucleotide(s) to which the first linker is attached is the nucleobase of a nucleotide at position n, preferably a thymine nucleobase. 74. A detection probe according to aspect 73, wherein: A. the second linker is attached to a chemical group at nucleotide position n+1 in the oligonucleotide(s); or B. the second linker is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), wherein x is an integer of 2 or more. 75. A detection probe according to any one of aspects 72 to 74, wherein the chemical group of the oligonucleotide(s) to which the second linker is attached is the nucleobase of a nucleotide, preferably a thymine nucleobase. 76. A detection probe according to aspect 70, wherein the second linker is attached to a chemical group which is attached to the terminal nucleotide position at the 5’ end of the oligonucleotide(s), preferably wherein the chemical group is a phosphate group. 77. A detection probe according to any one of aspects 61 to 68, wherein the probe comprises two oligonucleotides, and wherein: 1) the signal-promoting molecule is tethered to a first oligonucleotide by a first linker which is attached to a first position on the signal-promoting molecule and to a chemical group of the terminal nucleotide at the 3’ end of the first oligonucleotide, preferably to the 3’ terminal phosphate group of the first oligonucleotide; and 2) the signal-promoting molecule is tethered to a second oligonucleotide by a second linker which is attached to a second position on the signal-promoting molecule and to a chemical group of the terminal nucleotide at the 3’ end of the second oligonucleotide, preferably to the 3’ terminal phosphate group of the second oligonucleotide; and further wherein: A. the chemical group of the first oligonucleotide to which the first linker is attached, preferably the 3’ terminal phosphate group, comprises a first cleavage site, and the chemical group of the second oligonucleotide to which the second linker is attached, preferably the 3’ terminal phosphate group, comprises a second cleavage site; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage sites thereby producing a detectible signal. 78. A detection probe according to aspect 69, wherein: A. the signal-promoting molecule is a quencher which is tethered to the oligonucleotide(s) by a linker which is attached to the quencher and to a chemical group of the terminal nucleotide at the 3’ end of the oligonucleotide(s), preferably to the 3’ terminal phosphate group, at nucleotide position n of the oligonucleotide(s); and B. the probe further comprises a fluorophore which is tethered to the oligonucleotide(s) by a further linker which is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), provided that fluorescence emission from the fluorophore is quenched by the quencher; wherein the terminal nucleotide position at the 3’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 5’ end of the oligonucleotide(s) are defined as n+x where x is an integer of 0 or more; and when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site whereupon the quencher is separated from the oligonucleotide(s) and a detectible fluorescence emission signal is thereby produced by the fluorophore. 79. A detection probe according to aspect 78, wherein: A. the further linker is attached to a chemical group at nucleotide position n+0 in the oligonucleotide(s); or B. the further linker is attached to a chemical group at nucleotide position n+1 in the oligonucleotide(s); or C. the further linker is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), wherein x = 2 or more. 80. A detection probe according to aspect 79, wherein the chemical group of the oligonucleotide(s) to which the further linker is attached is a nucleobase, preferably a thymine nucleobase. 81. A detection probe according to aspect 69, wherein: A. the signal-promoting molecule is a fluorophore which is tethered to the oligonucleotide(s) by a linker which is attached to the fluorophore and to a chemical group of the terminal nucleotide at the 3’ end of the oligonucleotide(s), preferably to the 3’ terminal phosphate group at position n of the oligonucleotide(s); and B. the probe further comprises a quencher which is tethered to the oligonucleotide(s) by a further linker which is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), provided that fluorescence emission from the fluorophore is quenched by the quencher; wherein the terminal nucleotide position at the 3’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 5’ end of the oligonucleotide(s) are defined as n+x where x is an integer of 0 or more; and when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site whereupon the fluorophore is separated from the oligonucleotide(s) and a detectible fluorescence emission signal is thereby produced by the fluorophore. 82. A detection probe according to aspect 81, wherein: A. the further linker is attached to a chemical group at nucleotide position n+0 in the oligonucleotide(s); or B. the further linker is attached to a chemical group at nucleotide position n+1 in the oligonucleotide(s); or C. the further linker is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), wherein x = 2 or more. 83. A detection probe according to any one of aspects 78 to 82, wherein the chemical group of the oligonucleotide(s) to which the further linker is attached is a nucleobase, preferably a thymine nucleobase. 84. A detection probe according to any one of aspects 78 to 83, wherein: A. the quencher is a dark quencher, selected from the group consisting of Black Hole Quencher 0 (BHQO); Black Hole Quencher 1 (BHQ1); Black Hole Quencher 2 (BHQ2); Black Hole Quencher 3 (BHQ3); Black Berry Quencher 650 (BBQ-650); QSY-35; QSY-7; QSY-9; QSY-21; Eclipse quencher; and DABSYL (dimethylaminoazobenzenesulfonic acid); and B. the fluorophore is selected from the group consisting of Alexa 350; Pacific Blue; Marina Blue; Acridine; Edans; Coumarin; BODIPY 493 / 503; Cy2; BODIPY FL-X; DANSYL; Alexa 488; FAM; Oregon Green; Rhodamine Green-X; NBD-X; TET; Alexa 430; BODIPY R6G-X; JOE; Yakima Yellow; Alexa 532; HEX; R6G; Alexa 555; BODIPY TMR-X; Cy3; Alexa 546; TAMRA; Rhodamine Red-X; BODIPY 581 / 591; Redmond Red; Cy3.5; ROX; Alexa 568; Cal Red; Texas Red; BODIPY TR-X; Alexa 594; BODIPY 630 / 650-X; BODIPY 650 / 665-X; Alexa 647; Cy5; and Cy5.5. 85. A detection probe according to any one of aspects 78 to 84, wherein: A. the fluorophore is 6-carboxyfluorescein (6-FAM) and the quencher is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1;BHQ1); B. the fluorophore is tetrachlorofluorescein (TET) and the quencher is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1; BHQ1); C. the fluorophore is hexachlorofluorescein (HEX) and the quencher is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1; BHQ1); or D. the fluorophore is Carboxy-X-rhodamine (ROX) and the quencher is 4'-(4-Nitro-phenyldiazo)-2'-methoxy-5'-methoxy-azobenzene-4-ethylaminoethanol (Black Hole Quencher 2; BHQ2). 86. A detection probe according to aspect 69, wherein the probe has the structure: 1) wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, LI is the first linker, L2 is the second linker, and wherein BHQ1 is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1); wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; n=2, wherein n is the number of nucleotide positions relative to the 3’ end of the probe; LI is the first linker, L2 is the second linker attached to the nucleobase of the third nucleotide position relative the 3’ end of the probe; and wherein BHQ1 is 4-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1); or LI BHQ-1 Fluorescein wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, LI is the first linker, L2 is the second linker, and wherein BHQ1 is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1); or BHQ-1 LI wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; n=2, wherein n is the number of nucleotide positions relative to the 3’ end of the probe; LI is the first linker, L2 is the second linker attached to the nucleobase of the third nucleotide position relative the 3’ end of the probe; and wherein BHQ1 is 4-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1). 87. A detection probe according to any one of aspects 69 to 77, wherein the signalpromoting molecule is a polypeptide, and wherein when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal may be produced in a reaction which is dependent upon the polypeptide. 88. A detection probe according to aspect 87, wherein the polypeptide has enzymatic activity, and the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the polypeptide. 89. A detection probe according to aspect 88, wherein the polypeptide is a horseradish peroxidase (HRP) enzyme, preferably wherein the HRP enzyme has the amino acid sequence set forth in SEQ ID NO: 5. 90. A detection probe according to aspect 89, wherein the probe has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, L is the linker, and HRP is an HRP enzyme, preferably which has the amino acid sequence set forth in SEQ ID NO: 5. 91. A detection probe according to aspect 87, wherein the polypeptide is a component of an enzyme complex, a domain of an enzyme, a fragment of an enzyme or an enzyme cofactor, and the detectible signal is produced in a reaction which is dependent upon the polypeptide. 92. A detection probe according to aspect 91, wherein the polypeptide is a betagalactosidase alpha peptide, preferably having an amino acid sequence as set forth in SEQ ID NOS: 6 to 56. 93. A detection probe according to aspect 92, wherein the probe has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, LI is the first linker, and L2 is the second linker. 94. A detection probe according to aspect 87, wherein the polypeptide is an activator of an enzyme or an enzyme complex or cofactor, and the detectible signal is produced in a reaction which is dependent upon the polypeptide. 95. A detection probe according to aspect 94, wherein the polypeptide is Ml3 polypeptide, preferably having any one of the amino acid sequences set forth in SEQ ID NOS: 57, 58 and 59. 96. A detection probe according to aspect 95, wherein the probe has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. 97. A detection probe according to: A. aspect 69; or B. aspects 70 to 77; wherein the signal-promoting molecule is a small molecule, and wherein when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal may be produced in a reaction which is dependent upon the small molecule. 98. A detection probe according to aspect 97, wherein the small molecule promotes the formation of a molecular complex, such as a protein:protein complex, and the detectible signal is produced in a reaction which is dependent upon the formation of the molecular complex or protein:protein complex. 99. A detection probe according to aspect 98, wherein the small molecule is everolimus, which has the structure: 100. A detection probe according to aspect 99, wherein the probe has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. 101. A detection probe according to aspect 98, wherein the small molecule is rapamycin, having the structure: 102. A detection probe according to aspect 101, wherein the probe has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. 103. A detection probe according to aspect 97, wherein the small molecule promotes the activation of an enzyme or an enzyme complex, and the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex. 104. A detection probe according to aspect 103, wherein the signal-promoting molecule is methotrexate, having the structure: 105. A detection probe according to aspect 104, wherein the probe has the structure: 3’ wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. 106. A detection probe according to aspect 97, wherein the small molecule is a cofactor of an enzyme or an enzyme complex, and the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex. 107. A detection probe according to aspect 106, wherein the signal-promoting molecule is hemin, which has the structure: 108. A detection probe according to aspect 107, wherein the probe has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. 109. A composition comprising composition components: A. a RPA single-stranded DNA-binding protein (RPA-SSB) molecule; B a cleavage molecule; and C. a detection probe according to any one of aspects 61 to 108. 110. A recombinase polymerase amplification (RPA) reaction composition comprising composition components: A. RPA reaction components, including a RPA single-stranded DNA-binding protein (RPA-SSB) molecule, B a cleavage molecule; and C. a detection probe according to any one of aspects 61 to 108. 111. A kit comprising the kit components: A. a RPA single-stranded DNA-binding protein (RPA-SSB) molecule; B. a cleavage molecule; and C. a detection probe according to any one of aspects 61 to 108. 112. A recombinase polymerase amplification (RPA) reaction kit comprising the kit components: A. RPA reaction components, including a RPA single-stranded DNA-binding protein (RPA-SSB) molecule; B. a cleavage molecule; and C. a detection probe according to any one of aspects 61 to 108. 113. A composition according to aspect 109 or aspect 110, or a kit according to aspect 111 or aspect 112, wherein the composition components or kit components are provided in a dried form, optionally dried by air, dried using vacuum concentrator system or dried under an inert gas, or wherein the composition components or kit components are provided in a lyophilized (freeze-dried) form. 114. A composition according to aspect 109, a RPA reaction composition according to aspect 110, or a kit according to aspect 111, 112 or 113, wherein the single-stranded DNA-binding protein (RPA-SSB) molecule is selected from the group consisting of Gp32, E. coli SSB protein, phage T4 Gp32 protein, phage Rb69 Gp32, phage vBEcoMNBGl Gp32, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably the SSB molecule is Gp32 or phage vBEcoMNBGl Gp32. 115. A RPA reaction composition according to aspect 110, or a RPA reaction kit according to aspect 112 or 113, wherein in addition to the RPA-SSB, the RPA reaction components comprise a recombinase, a recombinase loading protein and a polymerase. 116. A RPA reaction composition, or a RPA reaction kit according to aspect 115, wherein: A. the recombinase is selected from the group consisting of UvsX, T4 UvsX, T6 UvsX, RBI8 UvsX, E.coli phage wV7 UvsX, Shigella phage CB8 UvsX, Shigella phage Shfl2 UvsX, E.coli phage ARI UvsX, phage vB_EcoM_G4507 UvsX, Shigella phage SHFML-11 UvsX, Escherichia phage vB EcoM DalCa UvsX, E. coli RecA, E. coli RadA, E. coli RadB, E. coli Rad 51 or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the recombinase agent is UvsX, more preferably Escherichia phage vBEcoMDalCa UvsX; B. the recombinase loading protein is selected from the group consisting of UvsY, E. coli RecO, E. coli RecR or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the recombinase loading protein is UvsY, more preferably Escherichia phage STO UvsY; C. the polymerase is a eukaryotic polymerase selected from the group consisting of pol-a, pol-P, pol-8, pol-s or any functional analog, homolog or derivative thereof, and any combination thereof; or the polymerase is a prokaryotic polymerase selected from the group consisting of Bacillus stearothermophilus polymerase I large fragment, Bacillus subtilis Pol I large fragment (Bsu polymerase), Listeria monocytogenes DNA polymerase I, S. aureus DNA polymerase I (Sau polymerase), E. coli DNA polymerase I Klenow fragment, E. coli DNA polymerase I, E. coli DNA polymerase II, E. coli DNA polymerase III, E. coli DNA polymerase IV, E. coli DNA polymerase V, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the polymerase is S. aureus DNA polymerase I (Sau polymerase) or Bacillus subtilis Pol I large fragment (Bsu polymerase); or the polymerase is a bacteriophage polymerase selected from the group consisting of bacteriophage T4 gp43 DNA polymerase, T7 DNA polymerase and Phi-29 DNA polymerase, or any functional analog, homolog or derivative thereof, and any combination thereof. 117. A composition according to aspect 109, 112 or 113, a RPA reaction composition according to aspect 110, 114, 115 or 116, or a kit according to any one of aspects 111 to 116, wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; wherein the cleavage molecule is Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. 118. A portable reaction device for performing a recombinase polymerase amplification (RPA) reaction, the device comprising: A. at least one sample application compartment; and B. at least one reagent compartment downstream of the at least one sample application compartment and in fluid communication therewith, wherein the reagent compartment comprises a RPA reaction composition according to any one of aspects 110, or 114 to 117, wherein the composition components of the RPA reaction composition are provided in a dried form, optionally dried by air, dried using vacuum concentrator system or dried under an inert gas, or wherein the composition components are provided in a lyophilized (freeze-dried) form. BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a general schematic showing the mechanism by which the probes described herein are unable to produce a signal (i.e. are ‘cloaked’) in the presence of a single-stranded binding protein and then, following amplification and incorporation into duplex DNA, are processed such that they are able to produce a detectable signal (i.e. are ‘uncloaked’). Figure 2 concerns a doubly modified probe comprising a 3’ fluorophore and 3’ quencher. (A) Shows the structure and mechanism of the probe. (B) Provides the sequences of the probe, target sequence, and forward and reverse primers. (C) Provides the results of the amplification assay. Figure 3 concerns a doubly modified probe comprising a 3 ’ fluorophore and nearby quencher. (A) Shows the structure and mechanism of the probe. (B) Provides the sequences of the probe, target sequence, and forward and reverse primers. (C) Provides the results of the amplification assay. Figure 4 depicts the structure and mechanism of a bead-oligo-HRP probe and processing of said probe by yeast TDP-1 (A). The sequences of the probe, target sequence, and forward and reverse primers are provided (B). The experimental set-up is depicted (C, lower panel) and the results of an amplification assay and TDP-1-mediated processing are provided (C, upper panel). Figure 5 shows the results of reconstitution reactions between cz / ?o-HRP and a hemin-oligo probe with and without nuclease (A). The wells contained: negative control (1), positive control (2), without nuclease (7-9), with nuclease (10-12). Figure 5 also shows the results of reconstitution reactions between apo-HRP and a hemin-oligo probe with and without nuclease as well as Gp32 protection of the oligo-hemin probe (B and C). (Nexo = nuclease.) Figure 6 shows the results of a control experiment to confirm that Gp32 is not influencing the colour change reaction of functional horse radish peroxidase. Addition of functional horse radish peroxidase in a solution that contains Gp32 causes a colour change. Figure 7 shows the results of a two-pot RPA reaction (Flu ANS; ntc = no template control; + = 3xl04 c / uL of FluA DNA) using the oligo-hemin / apo-HRP detection system. The reactions were first carried out in 30 uL with 180 nM of hemin-oligo FluANS probe at 42 °C. After 20 minutes the whole volume of each tube was transferred into a new tube containing all the components of the colorimetric reaction. A strong colour difference between ntc and positive is observed. Figure 8 shows the structures of the linear (A to C) and cyclic (D and E) oligoalpha-peptide probes synthesised and characterised by the inventors. Figure 9 shows the results of alpha complementation assays using the 5’-oligo-3’-N-alpha-peptide-C-term probe conjugate (‘N-terminus conjugate’ probe, as depicted in Figure 8A). Figure 10 shows the results of alpha complementation assays using the 5’-oligo-3’-C-alpha peptide-N term conjugate (£C-terminus conjugate’ probe, as depicted in Figure 8B) and the 5’-oligo-3’-N-alpha-peptide-C-3’-oligo-5’ conjugate (‘sandwich probe’, as depicted in Figure 8C). (A) Alpha complementation results using the C-terminus conjugate (left-hand panel) and the sandwich probe (right hand panel). In the left-hand panel: Tube 1: omega fragment; tube 2: omega fragment + probe; tube 3: omega fragment + probe + exo; tube 4: omega fragment + probe + exo + Gp32. In the right-hand panel: Tube 1: omega fragment + probe; Tube 2: omega fragment + probe + exo; Tube 3: omega fragment + probe + gp32; tube 4: omega fragment + probe + exo + Gp32. (B) Alpha complementation results using the C-terminus conjugate (right-hand panel) and sandwich probe (left-hand panel). In each panel, the first tube labelled (tube 2) is without Gp32 and the second tube labelled (tube 4) is with Gp32 after 2 hours. The sandwich probe gives a more optimised protection profile of the probe. See Example 5, Material and Methods for conditions. Figure 11 shows the results of chronoamperometry assays using the sandwich probe as depicted in Figure 8C. (A) Experiment demonstrating that the nuclease-driven release of alpha-peptide caused a rise of electrochemical signal due to alphacomplementation and subsequent beta-galactosidase catalytic hydrolysis of ANPG, which causes a release of 4-aminophenol, that is oxidized at the electrode. The orange trace shows that in the presence of Gp32 no signal is observed because Gp32 protects the probe from nuclease processing. Experiment was carried out in 25 mM Tris 7.5 mM Potassium acetate, 28 mM MgC12, 1.8 uM omega fragment, 20 nM alpha-peptide oligonucleotide probe. (B) Control experiments demonstrating that the electrochemical signal observed in (A) is due to beta-galactosidase. In the absence of omega fragment no signal is observed. In the presence of omega fragment a large increase of signal is observed upon addition of the probe. Figure 12 shows the results of RPA experiments looking at FluA amplification from DNA. denotes no template control (ntc); “+” denotes 3 x 104 c / uL. (A) Sandwich probe (as depicted in Figure 8C) was used at a concentration of 8.3 nM. The left- and right-hand panels correspond to two different replicates performed under the same conditions but with read out a slightly different timepoints. (B) Sandwich probe was used at a concentration of 50 nM. A stronger background develops with higher probe concentration. Figure 13 shows the results of an RPA amplification carried out in the presence of a 3’-3’ cyclic (circular) probe. Fluorescent substrate FAM digalactopyranoside was added to a final concentration of 15 uM and omega fragment to 1.8 uM. The oligo-alpha-peptide probe conjugate was used at a concentration of 40 nM. Figure 14 shows the results of an RPA amplification of Flu A from DNA carried out in the presence of the 3’-3’ oligo-alpha-peptide probe. The reaction was carried out under the following conditions: 5.5 % 35 K PEG; 1.8 uM omega fragment: 180 nM 3’-3’ oligo-alpha-peptide probe; 1 mM CPRG; and 28 mM MgOAc. Figure 15 shows the results of experiments to determine the limit of detection for using the 3’-3’ oligo-alpha peptide probe in RPA amplification reactions. (A) RPA was performed in the presence of PEG at varying copy / uL of FluB (NS) RNA, i.e. from 100 to 5 c / uL (left-hand panel) and from 1 to 0.1 c / uL (right-hand panel). (B) mRPA was performed to using FluA H1N1 target under acidic conditions (65 mM Tri cine pH 8.8 + 25 mM HC1) using 20 mM MgCh. The template concentration was varied from 10 c / uL to 1 c / uL. Figure 16 shows the results of chronoamperometry assays to assess the electrochemical detection of RPA amplification using the 3’-3’ oligo-alpha-peptide probe. Chronoamperometry (+0.2 V vs. Ag / AgCl), 40 °C. (A) mRPA of FluB template RNA via alpha-complementation dependent ANPG oxidation performed under the following conditions: 1.8 pM omega fragment, 120 nM probe, 20 mM MgOAc, 1%-y-cyclodextrin, 25 mM tris acetate, 25 mM ANPG, 2.5 mM ATP (neutral conditions). (B) mRPA of FluAHINI template RNA via alpha-complementation dependent ANPG oxidation performed under the following conditions: 1.8 pM omega fragment, 120 nM probe, 20 mM MgOAc, 1%-y-cyclodextrin, 25 mM tris acetate, 25 mM ANPG, 2.5 mM ATP (neutral conditions). DETAILED DESCRIPTION Probe Mechanism of Action Disclosed herein are new detection probes which are suitable for use in detecting a target nucleic acid sequence of interest in a test solution, the test solution comprising a recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB), a cleavage molecule and a target nucleic acid sequence of interest, preferably a DNA sequence of interest. The detection probes of the invention are further suitable for use in detecting a target nucleic acid sequence of interest in a recombinase polymerase amplification (RPA) reaction mixture, preferably a DNA sequence of interest. Detection probes which are not suitable for detecting a target nucleic acid sequence of interest in a test solution, as outlined above, or which are not suitable for detecting a target nucleic acid sequence of interest in an RPA reaction process, as outlined above do not fall within the scope of the present invention. The invention also relates to methods for detecting a target nucleic acid sequence of interest in a test solution, as described and defined further herein. Previous RPA detection probes have exploited the capability of certain nucleases to cleave the phosphodiester backbone of an oligonucleotide portion of the probe when the probe is hybridised to its target sequence. Cleavage produces a detectable signal, for example by separating a quencher and a fluorophore that were positioned in close proximity and engaged in a FRET interaction on the probe before cleavage. Previously-described RPA Fpg probes utilise the action of Escherichia coli formamidopyrimidine DNA glycosylase (Fpg). This enzyme catalyses the successive cleavage of the phosphodi ester bonds of the oligonucleotide, first on the 3 '-side and then on the 5'-side of an apurinic / apyrimidinic site (abasic site or AP site), to generate 5'- and 3'-phosphate ends respectively, thereby excising the abasic residue or abasic nucleotide from the oligonucleotide (Bhagwat et al, 1996, Biochemistry, 35(2), pp 659-665). In Fpg probes, typically, a signal-promoting molecule, such as a fluorophore, is linked to an abasic residue or nucleotide of the probe, such as the sugar molecule of an abasic nucleotide. The fluorophore is positioned in close proximity to a quencher, which is linked to a residue or nucleotide which is not an abasic residue or abasic nucleotide. When the probe hybridises to its target sequence, Fpg cleaves the phosphodiester backbone of the oligonucleotide at the 3'-side and then at the 5'-side of the abasic residue or nucleotide. This leads to the excision from the oligonucleotide of the abasic residue or nucleotide to which the fluorophore is linked, thereby resulting in a detectible signal. The linker itself is not cleaved. In Fpg probes, typically the quencher is linked to the oligonucleotide proximal to its 5’ end, and the fluorophore which is linked to the abasic residue or nucleotide is positioned on the 3’ side of the oligonucleotide relative to the quencher. Previously-described RPA Exo probes utilise the action of Escherichia coli Exonuclease III (Exo III), specifically the apurinic / apyrimidinic (AP) endonuclease activity, not the phosphatase / exonuclease activity, of this enzyme. The AP endonuclease activity of this enzyme catalyses the cleavage of the phosphodiester bond of the oligonucleotide on the 5'-side of an abasic site, thus generating a single internal cut in the phosphodiester backbone (Shida et al, 1996, Nucleic Acids Res., 24(22), pp 4572^4576). In Exo probes, typically, a signal-promoting molecule, such as a fluorophore, is linked to a residue or nucleotide of the oligonucleotide which is not an abasic residue or abasic nucleotide. The fluorophore is positioned in close proximity to a quencher, which is also linked to a residue or nucleotide which is not an abasic residue or nucleotide. The probe is structured so that the oligonucleotide has an abasic residue or abasic nucleotide positioned in between the positions occupied by the residues or nucleotides to which the fluorophore and quencher are linked. Tn Exo probes, typically an abasic residue is used which is a tetrahydrofuran (THF) base analog. Typically, the fluorophore is linked to the oligonucleotide via a residue or nucleotide proximal to the 5’ end of the oligonucleotide, and the quencher is positioned on the 3’ side of the oligonucleotide relative to the fluorophore, with the abasic residue positioned in between. When the probe hybridises to its target sequence, Exonuclease III cleaves the phosphodiester backbone on the 5'-side of the abasic residue, i.e. via the enzyme’s apurinic / apyrimidinic (AP) endonuclease activity. Typically, the portion of the oligonucleotide to which the quencher is linked can be dissociated from the target nucleic acid strand, and the portion of the oligonucleotide to which the fluorophore is linked remains hybridised to the target nucleic acid strand. Separation of the fluorophore and the quencher leads to the production of a detectible signal. The linkers which attach the fluorophore and quencher to the oligonucleotides are not themselves cleaved. In contrast to probes such as Fpg and Exo probes, in the detection probes of the present invention a signal-promoting molecule is attached to the oligonucleotide(s) by one or more linkers. In the probes of the present invention the linker(s) is not attached to an abasic nucleotide or an abasic residue. The linker(s) is not attached to a chemical group of an abasic nucleotide or abasic residue. The linker(s) is not attached to the oligonucleotide(s) at a nucleotide or residue position adjacent to a position in the oligonucleotide(s) which is occupied by an abasic nucleotide or an abasic residue. By adjacent, it is meant within 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotide or residue positions in the oligonucleotide(s) from a position which is occupied by an abasic nucleotide or an abasic residue. In the probes of the present invention the signal-promoting molecule is tethered to the oligonucleotide(s) via at least one linker which is attached to a chemical group of the oligonucleotide(s) and which thereby defines a cleavage site on the oligonucleotide, wherein the cleavage site is susceptible to cleavage mediated by phosphatase or exonuclease activity when contacted with a cleavage molecule having phosphatase or exonuclease activity. Conversely, in the probes of the present invention the signal-promoting molecule is tethered to the oligonucleotide(s) via at least one linker which is attached to a chemical group of the oligonucleotide(s) and which thereby defines a cleavage site on the oligonucleotide, wherein the cleavage site is not susceptible to cleavage mediated by apurinic / apyrimidinic (AP) endonuclease activity if contacted with a cleavage molecule having apurinic / apyrimidinic (AP) endonuclease activity. In the probes of the present invention, provided that the cleavage site is susceptible to cleavage mediated by phosphatase or exonuclease activity, and not to cleavage mediated by apurinic / apyrimidinic (AP) endonuclease activity, the linker(s) defining the cleavage site may be attached to the nucleotide or residue of the oligonucleotide at a phosphate group of the nucleotide or residue. The linker may be attached to the sugar of the nucleotide or residue of the oligonucleotide. The linker may be attached to the base of the nucleotide or residue of the oligonucleotide. When the probe is present in a test solution comprising a recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB), a cleavage molecule and a target nucleic acid sequence of interest: 1. when the oligonucleotide(s) is not hybridised with the target sequence, cleavage at the cleavage site by the cleavage molecule is inhibited and production of a detectible signal is thereby repressed; and 2. upon hybridisation of the oligonucleotide(s) with the target sequence, the cleavage molecule cleaves at the cleavage site, thereby producing a detectible signal. Importantly, in contrast to probes such as Fpg and Exo probes, the provision of a detectible signal in the probes of the invention following hybridisation of the oligonucleotide with the target sequence is not dependent upon a cleavage mechanism that is dependent upon the presence of an apurinic / apyrimidinic nucleotide or residue (also referred to as an abasic site or an apurinic / apyrimidinic (AP) site) or a cleavage mechanism that is dependent upon the presence of a mismatch in the oligonucleotide; e.g.: 1. is not dependent upon cleavage of the oligonucleotide(s) at an apurinic / apyrimidinic site (abasic site) of the oligonucleotide(s), e.g. at a 3'-side of an abasic site and / or at a 5'-side of the abasic site, such as at a position in the oligonucleotide(s) occupied by an abasic residue or an abasic nucleotide; 2. is not dependent upon cleavage of the oligonucleotide(s) at a mismatch site; or 3. is not dependent upon cleavage of the oligonucleotide(s) at a site comprising an abasic furan, such as tetrahydrofuran (THF). Accordingly, the probes of the invention are not compatible with the action of the apurinic / apyrimidinic (AP) endonuclease activity of Formamidopyrimidine DNA glycosylase or Exonuclease III. A probe of the invention can be configured to achieve these functional attributes. For example, the linker which attaches the signal-promoting molecule, such as a fluorophore or quencher, to the oligonucleotide and which defines the cleavage site is not attached to an abasic residue or an abasic nucleotide of the oligonucleotide, e.g. the sugar molecule of an abasic nucleotide. The linker which attaches the signal-promoting molecule, such as a fluorophore or quencher, to the oligonucleotide and which defines the cleavage site may not be attached to the oligonucleotide at a position adjacent to a position in the oligonucleotide which is occupied by an abasic residue or an abasic nucleotide. The probes of the invention are suitable for use in RPA reactions because they fail to provide a detectible signal when the oligonucleotide is not hybridised with the target sequence. However, when the oligonucleotide is hybridised with the target sequence e.g. during RPA cycles, a detectible signal can be produced. RPA reactions require the use of an RPA single-stranded DNA-binding protein (RPA-SSB) molecule, typically Gp32. The RPA-SSB will bind to the oligonucleotide of the probe of the invention since the probe comprises a single-stranded portion comprising a sequence which is complementary to a target nucleic acid sequence of interest. The RPA-SSB will dissociate from the oligonucleotide of the probe of the invention when the single-stranded portion of the probe hybridises with the target sequence of interest to form a double-stranded structure. A signal-promoting molecule is attached to the oligonucleotide(s) of the probe via at least one linker comprising a cleavage site. Without being bound by theory, but nevertheless consistent with the data described herein (see Example 3), the inventors believe that when the oligonucleotide is not hybridised with the target sequence, binding of the RPA-SSB to the oligonucleotide prevents the cleavage molecule from gaining access to the cleavage site. Consequently, no detectible signal is produced. However, when the oligonucleotide is hybridised with the target sequence, the RPA-SSB is dissociated from the oligonucleotide, thus allowing the cleavage molecule to gain access to the cleavage site. Consequently, a detectible signal is produced. The cleavage molecule which initially performs cleavage at the cleavage site is an enzyme having phosphatase and / or exonuclease activity, as further described and defined herein. Cleavage at the cleavage site may occurs by hydrolysis of the phosphomonoester bond which attaches a phosphate group to the remainder of the oligonucleotide, preferably the terminal phosphate group at the 3’ terminal end of the oligonucleotide. Without wishing to be bound by theory, cleavage at the cleavage site provides a detectible signal depending upon the nature of the signal-promoting molecule and how the signal-promoting molecule is linked to the oligonucleotide. For example, the signal-promoting molecule may be a fluorophore attached to a terminal phosphate group of the oligonucleotide, e.g. at the 3’ terminal end, by a single linker, and wherein a quencher is also attached to the oligonucleotide by a separate linker, and functions to quench the fluorescence emission of the fluorophore via a FRET interaction. Cleavage of the terminal phosphate group leads to the disruption of the FRET interaction, such that the quencher is no longer able to quench the fluorescence emission of the fluorophore. In such a situation, cleavage at the cleavage site by the cleavage molecule (phosphatase / exonuclease) will separate the signal-promoting molecule (fluorophore) from the oligonucleotide. In an alternative embodiment, the signal-promoting molecule may be a polypeptide which comprises or consists of a beta-galactosidase alpha peptide, and which is attached to the oligonucleotide by one or two linkers. If two linkers are use, a first linker may be attached to the polypeptide at a first amino acid position of the polypeptide and the second linker may be attached to the polypeptide at a second amino acid position of the polypeptide. The first linker may be attached to a terminal phosphate group of the oligonucleotide, e.g. at the 3’ terminal end, and the second linker may be attached to the oligonucleotide at a different position, such as attached to the nucleobase of the 3’ terminal nucleotide. As shown in the examples herein, such a probe does not provide a detectible signal when it is not hybridised to the target nucleic acid sequence of interest. This is because the RPA-SSB prevents the cleavage molecule from gaining access to the cleavage site. However, when the probe is hybridised to the target nucleic acid sequence of interest, the probe will provide a detectible signal. This is because the RPA-SSB no longer prevents the cleavage molecule from gaining access to the cleavage site. In such a situation, cleavage at the cleavage site by the cleavage molecule (phosphatase / exonuclease) will separate the first linker from the oligonucleotide. This can allow the signal-promoting molecule (beta-galactosidase alpha peptide) to come into contact with beta-galactosidase omega fragment (omega peptide) in solution to form betagalactosidase holoenzyme which can be detected. Without wishing to be bound by theory, the inventors believe that merely a single cleavage reaction to separate the first linker from the oligonucleotide is required to allow the beta-galactosidase alpha peptide to come into contact with beta-galactosidase omega fragment to form beta-galactosidase holoenzyme which can be detected. In such a situation, the signal-promoting molecule (betagalactosidase alpha peptide) may remain tethered to the oligonucleotide (via the second linker), i.e. is liberated relative to the oligonucleotide, and can still produce a detectible signal. A second cleavage reaction by the same cleavage molecule may occur to separate the second linker from the oligonucleotide. In such a situation, the signal-promoting molecule (beta-galactosidase alpha peptide) may be separated from the oligonucleotide and produce the detectible signal. Based on the knowledge of the invention, and the exemplary probe structures described and defined herein, a user will be able to configure a detection probe such that in a test solution comprising RPA-SSB molecules: i. when the oligonucleotide(s) is not hybridised with the target sequence, cleavage at the cleavage site is inhibited and production of a detectible signal is thereby repressed, and ii. upon hybridisation of the oligonucleotide(s) with the target sequence, the cleavage molecule cleaves at the cleavage site, thereby producing a detectible signal. In the probes of the invention, preferably the at least one linker which defines the cleavage site and which tethers the signal-promoting molecule to the oligonucleotide(s) of the probe, is attached to the sign al-promoting molecule and to the terminal phosphate group at the 3’ end of the oligonucleotide. Accordingly, the terminal phosphate group at the 3’ end of the probe comprises the cleavage site. Alternatively, in other probes of the invention, the at least one linker which defines the cleavage site and which tethers the signal-promoting molecule to the oligonucleotide(s) of the probe, is attached to the signal-promoting molecule and to the oligonucleotide at a position other than the terminal phosphate group at the 3’ end of the probe. Accordingly, the terminal phosphate group at the 3’ end of the probe does not comprise the cleavage site. In such an alternative probe structure, the terminal phosphate group at the 3’ end of the probe is susceptible to initial cleavage by the cleavage molecule via the phosphatase activity of the cleavage molecule. Subsequently, the cleavage molecule cleaves at the cleavage site via the exonuclease activity of the cleavage molecule. Oligonucleotide The detection probes of the invention comprise one or two oligonucleotides. As used herein the term “oligonucleotide” refers to a single-stranded multimer of nucleotide residues, optionally including non-nucleotide residues. An oligonucleotide can be defined as comprising a sequence of residues. A residue is the chemical entity which occupies a given position in the oligonucleotide sequence. An oligonucleotide portion of the probe will comprise a sequence of deoxyribonucl eotide residues. However, it is not a requirement that every position in the oligonucleotide portion of the probe must necessarily be occupied by a deoxyribonucleotide residue. Provided that the probe is capable of hybridising to the target DNA sequence of interest and comprises a functional repressible cleavage-dependent signalling system as described and defined further herein, then it may be possible to tolerate residues which are not deoxyribonucleotide residues. Accordingly, one or more positions in the oligonucleotide may be occupied by an abasic residue, provided that cleavage at the cleavage site is not dependent upon the presence of any such abasic residue, as discussed further herein. One or more positions in the oligonucleotide may be occupied by a locked nucleic acid residue or bridged nucleic acid residue. One or more positions in the oligonucleotide may be occupied by an unlocked nucleic acid residue. One or more positions in the oligonucleotide may be occupied by a peptide nucleic acid residue. In any oligonucleotide of any one of the probes described and defined herein, 90% of the oligonucleotide residue positions may be deoxyribonucleotide residues. In any oligonucleotide of any one of the probes described and defined herein, 91%, 92%, 93%, 94%, 95%, 96%, 97% ,98%, 99%, or 100% of the oligonucleotide residue positions may be deoxyribonucleotide residues. Optionally, any oligonucleotide of any one of the probes described and defined herein may comprise one or more abasic / apurinic residues along its length, provided that cleavage at the cleavage site is not dependent upon the presence of any such abasic / apurinic residues, as discussed further herein. Alternatively, any oligonucleotide of any one of the probes described and defined herein may comprise no abasic / apurinic residues along its length. Preferably, any oligonucleotide of any one of the probes described and defined herein comprises a deoxyribonucl eotide residue at each position along its length. Single stranded portion The detection probes of the invention comprise one or two oligonucleotides. The oligonucleotide(s) of the probe comprises a single-stranded portion comprising a sequence which is complementary to a target nucleic acid sequence of interest, preferably a DNA sequence of interest. The oligonucleotide(s) of the probe preferably consist of a single-stranded portion, i.e. in the probes of the invention the oligonucleotide(s) are preferably entirely single-stranded. Complementarity and bindins characteristics Because the oligonucleotide comprises a single-stranded portion comprising a sequence which is complementary to a target nucleic acid sequence of interest, the probe is structured so that it is capable of hybridising to the target nucleic acid sequence of interest by standard Watson-Crick base paring under appropriate conditions. The portion of the oligonucleotide which is complementary to a target nucleic acid sequence of interest may extend along the entire length of the oligonucleotide. Accordingly, an oligonucleotide of the probe may comprise or consist of a single-stranded portion which consists of a sequence which is complementary to a target nucleic acid sequence of interest. Alternatively, the portion of the oligonucleotide which is complementary to a target DNA sequence of interest may not necessarily extend along the entire length of the oligonucleotide. An oligonucleotide of the probe may comprise or consist of a singlestranded portion which comprises a sequence which is complementary to a target nucleic acid sequence of interest. The single-stranded portion of such an oligonucleotide may comprise other sequences which are not complementary to the target DNA sequence of interest and may be included in the oligonucleotide for purposes other than target DNA sequence recognition. It is not a requirement that the sequence which is complementary to the target DNA sequence of interest (target recognition sequence) hybridises with the target sequence in such a way that every position along the length of the target recognition sequence must necessarily be occupied with a nucleotide which engages in Watson-Crick base paring with a complementary nucleotide in the target strand. It is merely a requirement that the target recognition sequence is capable of hybridising to the target DNA sequence of interest under appropriate conditions. Accordingly, mismatches between nucleotides in the target strand and corresponding positions in the single-stranded portion of the probe may be tolerated, provided that the target recognition sequence is capable of hybridising to the target nucleic acid sequence of interest under appropriate conditions and further provided that cleavage at the cleavage site is not dependent upon the presence of any such mismatches, as discussed further herein. Length A detection probe according to the invention may be any suitable length provided that it is capable of providing the functional attributes described. In particular, provided that the probe comprises a repressible cleavage-dependent signalling system as detailed herein and which is dependent upon a recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB). The length of each of the one or two oligonucleotides may be chosen by the user to fit the particular circumstances of operation and is therefore not critical. The length of each of the one or two oligonucleotides may be about 20 to 70 nucleotide positions in length, about 25 to 65 nucleotide positions in length, preferably between about 30 to 60 nucleotide positions in length. Linkers A vast array of different chemistries are available to the user in order to tether signal-promoting molecules to oligonucleotides. One very general and popular method is “click chemistry”. Several types of click chemistry are available. For example, a free amino group may be provided on the signalpromoting molecule and a terminal azide group may be provided on the oligonucleotide. Alternatively, a free amino group may be provided on the oligonucleotide and a terminal azide group may be provided on the signal-promoting molecule. The free amino group can react, via an amidation reaction, e.g. with an N-hydroxysuccinimide (NHS) functionalised bicyclononyne (BCN) to create a BCN-functionalised position. The azide group can then be covalently attached, e.g. via a copper-free click chemistry, to the BCN-functionalised position. DBCO (dibenzocyclooctyne) click chemistry provides alternative methods. In these methods, a DBCO compound can be used to activate (functionalise) one molecule, and this is then reacted with the other molecule which has been activated / functionalised with an azide group. Reaction leads to the conjugation of the two molecules which become joined via a triazole linker. Click chemistry is used extensively to conjugate molecules for a wide range of biological applications and has wide and versatile applicability (for comprehensive reviews see Chio et al. “Click Chemistry Conjugations”, Methods Mol. Biol. 2020; 2078: pp 83-97; Fantoni et al. “A Hitchhiker’s Guide to Click-Chemistry with Nucleic Acids”. Chem. Rev. 2021, 121(12), pp 7122-7154). Many other chemistries are available for conjugation of molecules following the introduction of reactive groups, such as a reactive primary amine group or a reactive thiol group (for a comprehensive review see Spicer et al. “Achieving Controlled Biomolecule-Biomaterial Conjugation”, Chem. Rev. 2018, 118, pp 7702-7743) The linker chemistry can therefore be chosen by the user depending upon the specific signal-promoting molecule(s) to be tethered to the oligonucleotide(s) of the probe, and depending upon the specific oligonucleotide attachment position desired. Some nonlimiting examples are provided below. Linkers for attachment to 3 ’ terminal phosphate In any of the probes of the invention as described and defined herein wherein a linker is attached to the 3’ terminal phosphate group of an oligonucleotide of the probe, the linker may optionally have any one of the structures as set out in Table LI below. Table LI - exemplary linkers for attachment to the 3’ terminal phosphate group. The structures show the oligonucleotide of the probe, the 5’ end of the probe and the 3’ terminal phosphate group followed by the structure of the linker. Structure Chemistry f J p ’'OVO' L' HN < \ \ „-'N, Attachment to the 3’ terminal phosphate of the oligonucleotide via SPAAC (DBCO) reaction. (F cfVcF 'y^ "oh ° HN y-D H2N Attachment via introduction of a primary amine on the 3’ terminal phosphate of the oligonucleotide. 0" S'-oligamicfeeMe x p 'G'sf O" 0 Attachment via introduction of a primary amine on the 3’ terminal phosphate of the oligonucleotide. The carbon chain length can vary typically from C2 to C12 or a higher length. 0" &'Oi^C>nM^SK>ti^O—0 "P- O"z ' MH?. 6 Attachment via introduction of a primary amine on the 3 ’ terminal phosphate of the oligonucleotide. The carbon chain length can vary typically from C2 to C12 or a higher length. O’ s . -x .--^ NH> b\sl-yoniK:kKjfidB—0~P~0' V" '"' 6 ; OH Attachment via introduction of a primary amine on the 3 ’ terminal phosphate of the oligonucleotide. The carbon chain length can vary typically from C2 to C12 or a higher length. 0" 0H -A i : A .--..: 7 7^---,..,,:,,, 6 ' \ ZsA ?? V Z .-;M CH HN -v ■ >k.. / $ ~ Ax H -0 Fluorophore (e.g. FAM) attached to the 3 ’ terminal phosphate of the oligonucleotide. L ., O' -• >- « i o K NO / b^kjwwGks^ ..;X .N-JV XV' 7 i 1’ :■ a» o >-O,>' HO K ....: Quencher (e.g. BHQ-1) attached to the 3’ terminal phosphate of the oligonucleotide. 0. V'. q' HN*’0 o'''° -WiQor««feotice^ o. ^,0 x Ox .,0 HD o Attachment to the 3’ terminal phosphate of the oligonucleotide via copper-catalysed azi de-alkyne cycloaddition. CT SObganudeotRfe—o-'^ SH ;i -■ 'v O Attachment via introduction of a thiol on the 3 ’ terminal phosphate of the oligonucleotide. The carbon chain length can vary typically from C2 to C12 or a higher length. CT S^oliaonuoleohde — si ' O'" SH 0 Attachment via introduction of a thiol on the 3 ’ terminal phosphate of the oligonucleotide. See description above 0“ ---x S-Wjunuefeotitis p , y / :-, 0 Y'-'o'' y \.--' u ». o Attachment to the 3 ’ terminal phosphate of the oligonucleotide via introducing a maleimide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. In any of the probes of the invention as described and defined herein wherein a linker is attached to a chemical group at a nucleotide position of the oligonucleotide other than a phosphate group, e.g. attached to the nucleobase of a nucleotide, the linker may optionally have any one of the structures as set out in Table L2 below. Table L2 - exemplary linkers for attachment to chemical groups at nucleotide positions in the oligonucleotide (terminal or internal nucleotide positions). The structures show a nucleotide position in the oligonucleotide of the probe, with the structure of the linker shown attached to the nucleobase of the nucleotide. Structure Chemistry c i c i xz •Z - - P o Attachment to the nucleobase of an internal thymine nucleotide of the oligonucleotide via SPAAC (DBCO) reaction. h ....\ ..M- / ":. Hk k k--Z O' 6 ' "VktO Attachment to the nucleobase of an internal thymine nucleotide of the oligonucleotide via SPAAC (DBCO) reaction. 0 -.. a ^.Xnz HN .V-N 6" j 0” 0^^ —O~P-Oxy>^ 0- O ’ '"o-P-O--. d Attachment via introduction of a primary amine on the nucleobase (thymine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. NHg .Xx~ %^'N H o~ 9" \ ™o~p_Ox^X / o“ o "O-P-O^ S! 0 Attachment via introduction of a primary amine on the nucleobase (adenine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. nh3 p JMHz N' >■ N - • A H O"'" N" cr r\ 1 i / — “O~P~O, xk"P O 6 ' T>Xo^. !:l 0 Attachment via introduction of a primary amine on the nucleobase (cytosine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. o pun r .. hitX^n i ‘i '\ Pi N" 'N 1 O CT' \ —-o-A o” 6 ' Q-P-O^.. O Attachment via introduction of a primary amine on the nucleobase (guanine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. 9' H ,-V, A N. x-x -SH hn H o V-N O 1 cr cr\ Q": O " / 04-0^ & Attachment via introduction of a thiol on the nucleobase (thymine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. Attachment via > ,.-x X". .A. 4. ,.-■< ; '' '• <> introduction of a maleimide on the nucleobase (thymine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. nh2 X. N H / ' N" 'r X ...-. x-K -N. A 1 !< / ~-N“ '' ~ ~ If ■ Sf^ H 0 o" cr\ “O^P“O.xXU. / CT 0 'O~0CH.. 0 O X ..\\ '•<£■■ ‘x- N-0 7.....z Q Attachment via Introduction of a maleimide on the nucleobase (adenine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. ^4-.-A Attachment via W o H A •••^x -0 ..-- .-. x M A.-- --- X.-- *x.x -- M >.......- o introduction of a V / maleimide on the 0” G"“x >-. / 9' nucleobase (cytosine) 0 0‘4 0- G of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. O ____ H o « \ hk .- ii k HN-' ' V-K 0 >i '> 'q H ’N” '“N o" (r\ — Q—p..Q ...1".^.. / '0 o ' B G Attachment via Introduction of a maleimide on the nucleobase (guanine) of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. ' J o K 9' \ Attachment of a quencher (e.g. BHQ-1) to the nucleobase (thymine) of the oligonucleotide. ’O * J -. / Qf Attachment of a fluorophore (e.g. FAM) to the nucleobase (thymine) of the oligonucleotide. In any of the probes of the invention as described and defined herein wherein a linker is attached to the 5’ terminal end an oligonucleotide of the probe, the linker may optionally have any one of the structures as set out in Table L3 below. Table L3 - exemplary linkers for attachment to the 5’ terminal end. The structures show the linker attached to a phosphate group which is at the 5’ terminal end of the oligonucleotide of the probe (the oligonucleotide of the probe is not shown). Structure Chemistry A \ HN: V U x- x- 4 I Attachment to a phosphate group at the 5’ terminal of the oligonucleotide via SPAAC (DBCO) reaction. 4 4-A H 4 A ,x .--v .N O- P-Q.- o Y Y 6 0 'xm Attachment to a phosphate group at the 5’ terminal end of the oligonucleotide via SPAAC (DBCO) reaction. H2 N 0 o— 6 Attachment via introduction of a primary amine to a phosphate group at the 5’ terminal of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. o~ 6 Attachment via introduction of a thiol to a phosphate group at the 5’ terminal of the oligonucleotide for subsequent conjugation. The carbon chain length can vary typically from C2 to C12 or a higher length. □ p 0.. o Attachment to a phosphate group at the 5’ terminal of the oligonucleotide via copper-catalysed azidealkyne cycloaddition. In any of the probes of the invention as described and defined herein wherein a linker is attached to a primary amine of a chemical group at a nucleotide position an oligonucleotide of the probe, the linker may optionally be achieved via any one of the active esters as set out in Table L4 below. Table L4 - exemplary active esters for attachment to a primary amine. The structures show a BCN (bicyclo[6.1.0]nonyne) and DBCO active ester which can be attached to a primary amine group of the oligonucleotide of the probe for subsequent conjugation (the oligonucleotide of the probe is not shown). The attachment point can be at any position at the 5’ terminal end of the oligonucleotide, an internal position of the oligonucleotide or at any position at the 3’ terminal end of the oligonucleotide depending on the position of the primary amine at the preference of the user. Linker / Active Ester Structure Endo-BCN- NHS carbonate 00 ZC Endo-BCN- PEG2-NHS ester 9 $ Vx Il H o Endo-BCN-PEG3-NHS ester 0 r / o 0 0 Endo-BCN-PEG4-NHS ester o, 9 0 H O Endo-BCN-PEG8-NHS ester Endo-BCN-PEG12-NHS ester H O o DBCO-NHS ester cQo 0 DBCO-C5- NHS ester n 0 DBCO-C6- NHS ester ) o J IX p L^o DBCO-PEG1- NHS ester rOD . H o Vx 6 o DBCO-PEG2- NHS ester oQo M H 0 o 00^7 DBCO-PEG4- NHS ester ,A^ N H © a Q DBCO-PEG5- NHS ester H 9°VA O 0' DBCO- PEG12-NHS ester CXjO H O o DBCO- PEG24-NHS ester n DBCO- NHC0-PEG4- NHS ester rY Jit) O Q H kJ O DBCO- NHC0-PEG5- NHS ester n b DBCO- IN TlLv- PEG13-NHS ester OOO 0 H O DBCO-PEG5- TFP Ester ■ / •*•*•*•*■ Vi )1 J t:O / 0 <0 / \ Q ? ( 0 ? 0 -11 11 In any of the probes of the invention as described and defined herein, the linker may optionally have any one of the structures as set out in Table L5 below, as created via a peptide attachment. Table L5 exemplary linkers introduced via peptide attachment. The table shows the name and structure of the peptide attachment and the structure of the linker. Peptide Attachment Name Peptide Attachment Structure Linker Azido-acetyl-lysine p: A P + HN Nx - J 'N A -0H o p N:-—: / / A .....nz A hA ■ C ,N \..... / !~'N \..... / ' Azido-lysine +: p N N’ J MA^OH —N / H O .- / \\ r ’I N \_____ / Azidohomoalanine .....FT-oh H ci .... N ^A p r ?L N Azido-alanine * Al ......A / * O: ,.-7 \x . -N / P“.y Azido-norvaline * ,N A X. "11 r j ! P \.....z'"N' Azidoacetic acid (N-terminus labelling) o A ' --- OH p p .0 7 / ■—77 .•A A.... A' N X. / Azido-PEG4-acid (N-terminus labelling) >3 / 7 A -■AA 1 ’1 .N x....z'n Azido-PEG6-acid (N-terminus labelling) a \ _ / •V 1 H \™-7 Azido-PEGIO-acid (N-terminus labelling) I i -N V / '-N Azi do-PEG-NHS ester (N-terminus labelling) ( J 0 x>-n' ■ Z.„X H / % .....,d X / 1 ■■■^rNN i : ,N ’N y 7 Cysteine „,SH 1 QH —<■ y - H 1* 0 n oligo, ■I / □ "X s peptide jlig» ( )= Q <’■ \ r peptide lodo-acetyl-alpha peptide (N-terminus) O’ K A H oligo / < <’ Ao peptide The carbon chain can vary, typically from Cl to C12 or longer carbon chains. In any of the specific probe structures described, defined and exemplified herein wherein a peptide-triazole linkage is depicted, the linkage may change in alternative embodiments where different linker chemistries are employed for the purposes of conjugating (tethering) the signal-promoting molecule to the oligonucleotide(s). Accordingly, a depicted peptide-triazole linkage may be replaced with any of the linkers depicted above and herein depending upon the conjugation chemistry, e.g: Signal-promoting molecule Signal-promoting molecule Cleavage Molecule The cleavage molecule is any molecule having phosphatase / exonuclease activity, and which is suitable to effect cleavage at the cleavage site by the action of the molecule’s phosphatase activity and / or exonuclease activity. Such a molecule may additionally intrinsically possess apurinic / apyrimidinic (AP) endonuclease activity, however the present probes are structured such that apurinic / apyrimidinic (AP) endonuclease activity cannot mediate cleavage at the cleavage site. Preferably the cleavage molecule may be Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. The amino acid sequence of Escherichia coli Exonuclease III defined by SEQ ID NO: 1; is set forth below: MKFVSFNINGLRARPHQLEAIVEKHQPDVIGLQETKVHDDMFPLEEVAKLG YNVFYHGQKGHYGVALLTKETPIAVRRGFPGDDEEAQRRIIMAEIPSLLGNVTVIN GYFPQGESRDHPIKFPAKAQFYQNLQNYLETELKRDNPVLIMGDMNISPTDLDIGI GEENRKRWLRTGKCSFLPEEREWMDRLMSWGLVDTFRHANPQTADRFSWFDYR SKGFDDNRGLRIDLLLASQPLAECCVETGIDYEIRSMEKPSDHAPVWATFRRAGEF KLAAALEHHHHHH. The amino acid sequence of or tyrosyl-DNA phosphodiesterase 1 (TDP-1) defined by SEQ ID NO: 2; is set forth below: MHHHHHHMMKITTWNVN S LN VRLPQ V QNLLADNPPDILVLQELKLDQDK FPAAALQMMGWHCVWSGQKTYNGVAIVSRSVPQDVHFGLPSLPDDPQRRVIAAT VGGVRVINVYCVNGEALDSPKFKYKEQWFAALTEFVRDEMTRHGKLVLLGDFNI APADADCYDPEKWYEKIHCSSVERQWFQNLLDLGLTDSLRQVHPEGAFYTWFDY RGAMFQRKLGLRIDHILVTSEMAAVLKDVRIDLETRALERPSDHAPVAAEFDL. The amino acid sequence of tyrosyl-DNA phosphodiesterase 1 (TDP-1) defined by SEQ ID NO: 3 (Saccharomyces cerevisiae TDP-1; yTDP-1) is set forth below: MSRETNFNGTKRKRSDVAEKVAQRWKSVRYSAEMENMA PVNSNNDSDDCVIVSESKIIDLTNQEQDLSERIGTNDTAKGAVFKLMKSDFYERED FMGEVEDMITLKDIFGTETLKRSILFSFQYELDFLLRQFHQNVENITIVGQKGTIMPI EARAMDATLAVILKKVKLIEITMPPFASHHTKLIINFYDNGECKIFLPSNNFTSMET NLPQQVCWCSPLLKIGKEGLPVPFKRSLIEYLNSYHLKDIDELITKSVEEVNFAPLS ELEFVYSTPSKFQSSGLLSFYNKLEKLSAGTSASDTAKHYLCQTSSIGTSLSRARDE NLWTHLMIPLFTGIMSPPAKDTAGRKKAEILPTNSLINEYSQRKIKPYIIFPTEQEFV TSPLKWSSSGWFHFQYLQKKSYYEMLRNKFKVFYKQDPAMVTRRRGTTPAHSKF YMHCATNSTGPCDASQVFKELEWCLYTSANLSQTAWGTVSRKPRNYEAGVLYHS RRLANTRKVTCRTFTRDRRGCAGNPTHVAVPFTLPVIPYDLAEDECFCLARHEND. The amino acid sequence of tyrosyl-DNA phosphodiesterase 1 (TDP-1) defined by SEQ ID NO: 4 (yTDP-1 - maltose binding protein (MBP) domain fusion protein) is set forth below: MGHHHHHHKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPD KLEEKFPQVAATGDGPDIIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDA VRYNGKLIAYPIAVEALSLIYNKDLLPNPPKTWEEIPALDKELKAKGKSALMFNLQ EPYFTWPLIAADGGYAFKYENGKYDIKDVGVDNAGAKAGLTFLVDLIKNKHMNA DTDYSIAEAAFNKGETAMTINGPWAWSNIDTSKVNYGVTVLPTFKGQPSKPFVGV LSAGINAASPNKELAKEFLENYLLTDEGLEAVNKDKPLGAVALKSYEEELVKDPRI AATMENAQKGEIMPNIPQMSAFWYAVRTAVINAASGRQTVNEALKDAQTGPRTG SLVPRGSASENLDFQGMSIYQEFMSRETNFNGTKRKRSDVAEKVAQRWKSVRYS AEMENMAPVNSNNDSDDCVIVSESKIIDLTNQEQDLSERIGTNDTAKGAVFKLMK SDFYEREDFMGEVEDMITLKDIFGTETLKRSILFSFQYELDFLLRQFHQNVENITIV GQKGTIMPIEARAMDATLAVILKKVKLIEITMPPFASHHTKLIINFYDNGECKIFLPS NNFTSMETNLPQQVCWCSPLLKIGKEGLPVPFKRSLIEYLNSYHLKDIDELITKSVE EVNFAPLSELEFVYSTPSKFQSSGLLSFYWLEKLSAGTSASDTAKHYLCQTSSIGT SLSRARDENLWTHLMIPLFTGIMSPPAKDTAGRKKAEILPTNSLINEYSQRKIKPYII FPTEQEF VTSPLKWS S SGWFHFQYLQKKS YYEMLRNKFKVF YKQDPAMVTRRRG TTPAHSKFYMHCATNSTGPCDASQVFKELEWCLYTSANLSQTAWGTVSRKPRNY EAGVLYHSRRLANTRKVTCRTFTRDRRGCAGNPTHVAVPFTLPVIPYDLAEDECF CLARHEND. Test Solution A detection probe of the invention is suitable for use in detecting a target nucleic acid sequence of interest in a test solution. The test solution comprises at least a recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB), a cleavage molecule and a target nucleic acid sequence of interest. As shown in Example 3, the inventors have identified that the presence of a RPA-SSB in the test solution is sufficient, together with the probe, cleavage molecule and target sequence, to provide for the repressible cleavage-dependent signalling system which characterises the probes of the invention. Accordingly, it is not necessary that the test solution actually comprises an RPA reaction mixture comprising all of the RPA reaction components required to support an RPA reaction. Nevertheless, the probes of the invention find particular application in the detection of target nucleic acid sequences of interest in RPA reactions and consequently a suitable test solution comprises: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes of the invention as described and defined herein; d. a target nucleic acid sequence of interest; and e. a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: i. a recombinase agent; ii. optionally a recombinase loading protein; iii. a polymerase; and iv. forward and reverse nucleic acid primers for amplification. Repressible Cleavage-Dependent Signalling System All detection probes described and defined herein comprise a repressible cleavagedependent signalling system. The signalling system is repressible as described in more detail herein in relation to probe mechanism of action. Thus, a probe of the invention will fail to provide a detectible signal when the oligonucleotide is not hybridised with the target sequence. This is because the recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB) molecule present in the test solution, typically Gp32, will bind to the oligonucleotide of the probe and prevent the cleavage molecule from gaining access to the cleavage site. However, when the oligonucleotide is hybridised with the target sequence, the RPA-SSB is dissociated from the oligonucleotide, thus allowing the cleavage molecule to gain access to the cleavage site and effect cleavage. Accordingly, the signalling system is repressed or inhibited in the test solution when the oligonucleotide is not hybridised with the target sequence The signalling system is de-repressed or activated when the oligonucleotide is hybridised with the target sequence in the test solution. The repressible / activatable nature of the probes via association and disassociation of the RPA-SSB and access of the cleavage molecule to the cleavage site, characterises the mechanism of action of the probes. Essential to the repressible cleavage-dependent signalling system is the use of a signal-promoting molecule, which is attached to the probe as described elsewhere herein. Upon access to the cleavage site, the cleavage molecule performs cleavage by the action of phosphatase / exonuclease activity, and not by the action of apurinic / apyrimidinic (AP) endonuclease activity. The probe is consequently structured so that phosphatase / exonuclease cleavage triggers the operation of the signal-promoting molecule and conversely so that apurinic / apyrimidinic (AP) endonuclease activity does not trigger the operation of the signal-promoting molecule. In view of the description herein, a user will readily be able to structure the probe to provide these effects. A wide range of signal-promoting molecules comprising various different repressible cleavage-dependent signalling system configurations have been designed, implemented and exemplified by the inventors. Signal-Promoting Molecule A signal-promoting molecule forming the repressible cleavage-dependent signalling system is any molecule which is capable of generating a detectible signal via a probe of the invention based on the mechanism of action described herein. As will be evident having regard to the exemplary systems described herein, the signal-promoting molecule may be capable of generating a detectible signal either directly or indirectly. The signal-promoting molecule may have the capability of generating a detectible signal intrinsically. An example of such a signal-promoting molecule is a fluorophore, and wherein the repressible cleavage-dependent signalling system further comprises a quencher. The fluorophore can be separated from the oligonucleotide following cleavage at the cleavage site by the cleavage molecule. Separation of the fluorophore from the oligonucleotide prevents the quencher from quenching the signal of the fluorophore, such that the fluorophore is then capable of generating a detectible signal. Alternatively, the signal-promoting molecule may itself lack the capability of generating a detectible signal intrinsically but is nevertheless capable of generating a detectible signal indirectly. An example of such a signal-promoting molecule is a quencher, a component of an enzyme complex, a domain of an enzyme, a fragment of an enzyme or an enzyme cofactor. For example, an enzyme component can be separated from or liberated relative to the oligonucleotide following cleavage at the cleavage site by the cleavage molecule. Separation or liberation of the enzyme component from the oligonucleotide allows the enzyme component to associate with other components of the enzyme to form a holoenzyme, wherein the holoenzyme is then capable of generating a detectible signal, e.g. a colorimetric signal. Various different signal-promoting molecules as components of cleavagedependent signalling systems are described below. Sisnal-Promotins Molecule — Fluorophore / Quencher A signal-promoting molecule may be a fluorophore or a quencher. Fluorophore As noted above, a signal-promoting molecule may be a fluorophore, and wherein the repressible cleavage-dependent signalling system further comprises a quencher tethered to the oligonucleotide. The quencher is positioned adjacent the fluorophore on the oligonucleotide such that the fluorophore and quencher engage in a FRET interaction. In this configuration, the quencher prevents the fluorophore from generating a detectible signal by fluorescence when the probe is in single-stranded form and not hybridised to the target sequence of interest in a reaction mixture comprising a RPA-SSB. The fluorophore is attached to the oligonucleotide(s) via at least one linker comprising a cleavage site. The fluorophore is separated from the oligonucleotide following cleavage at the cleavage site by the cleavage molecule when the probe is in double-stranded form and hybridised to the target sequence of interest in a reaction mixture comprising a RPA-SSB. Methods for detecting a target nucleic acid sequence of interest in a reaction mixture as described and defined herein comprise detecting the target sequence of interest by detecting a detectible signal produced by the signal-promoting molecule. Separation of the fluorophore from the oligonucleotide(s) prevents the quencher from quenching the fluorescence signal produced by the fluorophore, and therefore permits a detectible signal to be generated. In such a system the quencher may be tethered to the oligonucleotide(s) via at least one linker which comprises a cleavage site. Alternatively, the quencher may be tethered to the oligonucleotide(s) via at least one linker which does not comprise a cleavage site. Whether or not the quencher is linked to a cleavage site on the oligonucleotide is not relevant, since cleavage of the linker attaching the fluorophore will separate the fluorophore from the quencher whether or not the quencher remains attached to the oligonucleotide. Quencher The signal-promoting molecule may be a quencher, and wherein the repressible cleavage-dependent signalling system further comprises a fluorophore which is tethered to the oligonucleotide by a linker which does not comprise a cleavage site. The quencher is positioned adjacent the fluorophore on the oligonucleotide such that the fluorophore and quencher engage in a FRET interaction. In this configuration, the quencher prevents the fluorophore from generating a detectible signal by fluorescence when the probe is in single-stranded form and not hybridised to the target sequence of interest in a reaction mixture comprising a RPA-SSB. In such a system, the quencher is separated from the oligonucleotide following cleavage at the cleavage site by the cleavage molecule when the probe is in double-stranded form and hybridised to the target sequence of interest in a reaction mixture comprising a RPA-SSB. Separation of the quencher from the oligonucleotide prevents the quencher from quenching the fluorescence signal produced by the fluorophore, and therefore permits a detectible signal to be generated. Fluorophore / Quencher Positionins In such a repressible cleavage-dependent signalling system, the nucleotide positions on the oligonucleotide at which the quencher and the fluorophore are tethered are not critical, provided that at least one linker attaching the signal-promoting molecule, be it a fluorophore or a quencher, comprises a cleavage site and provided that the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that the fluorophore and quencher are positioned in close proximity in a FRET interaction, thereby allowing the quencher to quench the fluorescence signal from the fluorophore when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. A user can readily structure a probe such that at least one linker attaching the signal-promoting molecule, be it a fluorophore or a quencher, to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, the signal-promoting molecule, be it a fluorophore or a quencher, is tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, the signal-promoting molecule may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is a fluorophore or a quencher, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Fhwrophores, Quenchers and Pairs The table below provides a list of exemplary quenchers which may be used with the probes of the invention. Quencher Generic Name Quencher Chemical Name Black Hole quencher 0 4'-(2-methyl-phenyldiazo)-2'-methyl-azobenzene-4-ethylaminoethanol Black Hole quencher 1 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol Black Hole quencher 2 4'-(4-Nitro-phenyldiazo)-2'-methoxy-5'-methoxy-azobenzene-4-ethylaminoethanol Black Hole quencher 3 3 -Di ethyl ami no-5 -phenyl phenazium-7-di azob enzene-4-ethylaminoethanol Black berry quencher 650 6-((9-(( 1E)-(2,5 -dimethoxy-4-((4- nitrophenyl)diazenyl)phenyl)diazenyl)-julolidin-l-yl)oxy)hexan-1 -ol QSY-35 2-(4-((7-nitrobenzo[c] [ 1,2,5]oxadiazol-4-yl)amino)phenyl)acetic acid QSY-7 9-[2-( [4-[[( 2.5-di oxo-1 -pyrro!idinyl)oxy]carbonyl]-1 -piperidmyl]sulfonyl]phenyl]-3.6~bis(methylphenyl amino) iXHS ester) QSY-9 4-[[9-[2-[4-(2,5-dioxopyrrolidin-l- yl)oxycarbonylpiperidin-l-yl]sulfonylphenyl]-6-[methyl- (4-sulfonatophenyl)azaniumylidene]xanthen-3-yl]-methylamino]benzenesulfonate;hydron;chloride QSY-21 (2,5-dioxopyrrolidin-l-yl) l-[2-[3-(l,3-dihydroisoindol-2-ium-2-ylidene)-6-(l,3-dihydroisoindol-2-yl)xanthen-9-yl]phenyl]sulfonylpiperidine-4-carboxylate;chloride Eclipse 4-N-methyl-N-(4'-nitro-2'-chloroazobenzen-4-yl)-aminobutanamido-1 -(2-methoxy)-pyrrolidin-4-ol DABCYL 4-[4-(Dimethylamino)phenylazo]benzoic acid The table below provides a list of exemplary fluorophores which may be used with the probes of the invention. Fluorophore Generic Name Fluorophore Chemical Name Alexa 350 2H-l-Benzopyran-6-sulfonic acid, 7-amino-3-[2-[(2,5-dioxo-l-pyrrolidinyl)oxy]-2-oxoethyl]-4-methyl-2-oxo- (NHS ester) Pacific Blue 6,8-difluoro-7-hydroxy-2-oxo-2H-chromene-3-carboxylic acid Marina Blue 6,8-difluoro-7-hydroxy-4-methylcoumarin Acridine [4-[3-(2,5-dioxopyrrolidin-l-yl)oxy-3-oxopropyl]phenyl] 10-methylacri din-10-ium-9-carboxylate;trifluorom ethanesulfonate Edans 5-(2-aminoethylamino)naphthalene-l-sulfonic acid Coumarin 6-(ll-oxo-2,3,6,7-tetrahydro-lH,5H,llH-pyrano[2,3- f]pyrido[3,2,l-ij]quinoline-10-carboxamido)hexanoic acid BODIPY 493 / 503 l,3,5,7,8-pentamethyl-4,4-difluorro-4-bora-3a,4a-diaza-s-indacene Cy2 6-[2-[(E,3E)-3-(3-ethyl-l,3-benzoxazol-2-ylidene)prop-l-enyl]-l,3-benzoxazol-3-ium-3-yl]hexanoate BODIPY FL-X (2,5 -dioxopyrrolidin-1 -yl) 6-[3 -(2,2-difluoro-10,12-dimethyl-3 - aza-l-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca- 1 (12),4,6,8,10-pentaen-4-yl)propanoylamino]hexanoate DANSYL 5-(Dimethylamino)naphthalene-1 -sulfonyl chloride Alexa 488 2-(6-amino-3-iminio-4,5-disulfonato-3H-xanthen-9-yl)benzoic acid FAM 6-carboxyfluorescein Oregon Green 2-(2,7-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid Rhodamine Green-X 2-(6-amino-3-iminio-3H-xanthen-9-yl)benzoate NBD-X 6-((7-Nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino)hexanoic acid 7-Nitrobenzoxadiazole-6-aminohexanoic acid TET tetrachl orofluorescei n Alexa 430 [9-[6-(2,5-dioxopyrrolidin-l-yl)oxy-6-oxohexyl]-8,8-dimethyl-2-oxo-4-(trifluoromethyl)pyrano[3,2-g]quinolin-6- yl]methanesulfonate;triethylazanium BODIPY R6G-X 3-(4,4-Difluoro-5-phenyl-3a,4a-diaza-4-bora-s-indacen-3-yl)propionic acid JOE 6-carboxy-4',5'-dichloro-2',7'-dimethoxy-fluorescein Yakima Yellow 4,5-dichloro-2-(2,5-dichloro-6-hydroxy-4-methyl-3-oxo-4,9-dihydro-3 H-xanthen-9-yl )b enzoi c aci d Alexa 532 4-(7,8,8,16,16,17-hexamethyl-4,20-disulfo-2-oxa-6,18-diazapentacyclo[l 1.7.0.03,11.05,9.015,19]icosa- 1 (20),3,5,9,11,13,15(19)-heptaen-12-yl)benzoic acid UEV hexachl orofluorescei n R6G [9-(2-ethoxycarbonylphenyl)-6-(ethylamino)-2,7-dimethylxanthen-3 -yli dene] -ethyl azanium; chi ori de Alexa 555 4-(6-amino-3 -imino-4,5 -di sulfo-3 H-xanthen-9-yl)i sophthalic acid BODIPY TMR-X (2,5-dioxopyrrolidin-l-yl) 6-[3-[2,2-difluoro-12-(4-methoxyphenyl)-4,6-dimethyl-1 -aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,ll-pentaen-5-yl ] prop anoyl amino] hexanoate Cy3 1-propyl-3,3,3',3'-Tetramethylindocarbocyanine-l-propanoic acid Alexa 546 sodium 6-(2-carboxy-3,4,6-trichloro-5-{[2-({6-[(2,5-dioxopyrrolidin-1 -y l)oxy ] -6-oxohexyl} amino)-2-oxoethyl]thio}phenyl)-2,2,4,8,10,10-hexamethyl- 3,4,5 a, 8,9,10,11,12a-octahydro-2H-pyrano[3,2-g: 5,6-g']diquinolin-l-ium-12,14-disulfonate TAMRA Carboxytetramethylrhodamine Rhodamine Red-X 5-(5-carboxypentylsulfamoyl)-2-[3-(diethylamino)-6-diethylazaniumylidenexanthen-9-yl]benzenesulfonate BODIPY 581 / 591 11 -[2,2-Difluoro-12-[( lE,3E)-4-phenylbuta-1,3 -dienyl] -3-aza-1 -azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-l(12),4,6,8,10-pentaen-4-yl]undecanoic acid Redmond Red 7-hydroxy-2-(3-(4-hydroxy-2-(hydroxymethyl)pyrrolidin-l-yl)- 3 -oxopropyl)-3H-phenoxazin-3 -one Cy3.5 1 -propyl -3,3,3 ',3 '-tetramethyl-4,5 -benzindocarbocyanine chloride-1-propanoic acid ROX Carboxy-X-rhodamine Alexa 568 5-(2,5-dioxopyrrolidin-l-yl)oxycarbonyl-2-[7,7,19,19-tetramethyl-9,17-bis(sulfomethyl)-2-oxa-6,20- diazapentacyclo[12.8.0.03,12.05,10.016,21]docosa-1(14),3,5,8,10,12,15,17,21 -nonaen-13-yl]benzoic acid Cal Red 2-(3-oxa-23-aza-9- azoniaheptacyclo[l 7.7.1.15,9.02,17.04,15.023,27.013,28]octacos a-1 (27),2( 17),4,9(28), 13,15,18-heptaen-16-yl)benzoic acid;pentafluoro-X5-phosphane;fluoride Texas Red 5-chlorosulfonyl-2-(3-oxa-23-aza-9- azoniaheptacyclo[17.7.1.15’9.02’17.04’15.023,27 013’28]octacosa- 1 (27),2(17),4,9(28), 13,15,18-heptaen-16-yl)benzenesulfonate BODIPY TR-X (T-4)-[N-[6-[(2,5-Dioxo-l-pyrrolidinyl)oxy]-6-oxohexyl]-2-[4-[5-((5-(2-thienyl)-2H-pyrrol-2-ylidene-kappaN]methyl]-lH-pyrrol-2-yl-kappaN]phenoxy]acetamidato]difluoroboron Alexa 594 [13-[2-carboxy-4-(2,5-dioxopyrrolidin-l-yl)oxycarbonylphenyl]-6,7,7,19,19,20-hexamethyl- 17-(sulfomethyl)-2-oxa-20-aza-6-azoniapentacyclo[12.8.0.03,12.05,10.016,21]docosa- 1 (14),3,5,8,10,12,15,17,21 -nonaen-9-yl]methanesulfonate BODIPY 630 / 650-X (2,5-dioxopyrrolidin-l-yl) 6-[[2-[4-[(E)-2-(2,2-difluoro-12- thiophen-2-yl-3-aza-l-azonia-2- boranuidatricyclo[7.3.0.03,7]dodeca-l(12),4,6,8,10-pentaen-4-yl)ethenyl]phenoxy]acetyl]amino]hexanoate BODIPY 650 / 665-X (2,5-dioxopyrrolidin-l-yl) 6-[[2-[4-[(E)-2-[2,2-difluoro-12-(lH- pyrrol-2-yl)-3-aza-l-azonia-2- boranuidatricyclo[7.3.0.03,7]dodeca-l(12),4,6,8,10-pentaen-4-yl]ethenyl]phenoxy]acetyl]amino]hexanoate Alexa 647 3-[(2Z)-2-[(2E,4E)-5-[3,3-dimethyl-5-sulfo-l-(3- sulfopropyl)indol-l-ium-2-yl]penta-2,4-dienylidene]-3-[5-(2,5-dioxopyrrolidin-l-yl)oxy-5-oxopentyl]-3-methyl-5-sulfoindol-l-yl]propane-l -sulfonate Cy5 1 -propyl-3,3,3',3'-tetramethylindodicarbocyanine chloride-1 -propionic acid Cy5.5 l-propyl-3,3,3',3'-tetramethyl-4,5-benzindodicarbocyanine chloride-1-propanoic acid The table below provides a list of exemplary fluor ophore / quencher pairs which may be used with the probes of the invention. The symbol “x” denotes a specific combination of a fluorophore from the left column together with a quencher from the top row. Quenchers BHQ-0 BHQ-1 BHQ-2 BHQ-3 BBQ 650 QSY-35 QSY-7&9 QSY-21 Eclipse DABCYL Fluorophores Alexa 350 X X X Pacific Blue X X X Marina Blue X X X X Acridine X X X X Edans X X X X Coumarin X X X X BODIPY 493 / 503 X X X X Cy2 X X X BODIPY FL- X X X X DANSYL X Alexa 488 X FAM X Oregon Green X Rhodamine Green-X X NBD-X X TET X Alexa 430 X X BODIPY R6G-X X X JOE X X Yakima Yellow X X Alexa 532 X X HEX X X R6G X X Alexa 555 X X BODIPY TMR-X X X Cy3 X X Alexa 546 X X TAMRA X X Rhodamine Red-X X X BODIPY 581 / 591 X X Redmond Red X X Cy3.5 X ROX X Alexa 568 X Cal Red X Texas Red X BODIPY TR-X X Alexa 594 X BODIPY 630 / 650-X X BODIPY 650 / 665-X X X Alexa 647 X X Cy5 X X Cy5.5 X X NondJmiting Exemplary Probe Embodiments The detection probe may be a probe wherein the signal-promoting molecule is a fluorophore, or wherein the signal-promoting molecule is a quencher. The detection probe may be a probe wherein: A. the fluorophore is 6-carboxyfluorescein (6-FAM) and the quencher is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1;BHQ1); B. the fluorophore is tetrachlorofluorescein (TET) and the quencher is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1; BHQ1); C. the fluorophore is hexachlorofluorescein (HEX) and the quencher is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1; BHQ1); D. the fluorophore is Carboxy-X-rhodamine (ROX) and the quencher is 4'-(4-Nitro-phenyldiazo)-2'-methoxy-5'-methoxy-azobenzene-4-ethylaminoethanol (Black Hole Quencher 2; BHQ2); or E. the fluorophore and quencher pair is any other pair identified in the above table of exemplary fluorophore / quencher pairs which may be used with the probes of the invention. The detection probe may be a probe having the structure: 1) wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, LI is the first linker, L2 is the second linker, and wherein BHQ1 is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1); 2) Fluorescein 0W wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; n=2, wherein n is the number of nucleotide positions relative to the 3’ end of the probe; LI is the first linker, L2 is the second linker attached to the nucleobase of the third nucleotide position relative the 3’ end of the probe; and wherein BHQ1 is 4'-(2-Nitro-4-toluyldiazo)- 2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1); or 3) BHQ-1 wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, LI is the first linker, L2 is the second linker, and wherein BHQ1 is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1) and FAM is fluorescein; or BHQ-1 LI wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; n=2, wherein n is the number of nucleotide positions relative to the 3’ end of the probe; LI is the first linker, L2 is the second linker attached to the nucleobase of the third nucleotide position relative the 3’ end of the probe; and wherein BHQ1 is 4'-(2-Nitro-4-toluyldiazo)-2'-methoxy-5'-methyl-azobenzene-4-ethylaminoethanol (Black Hole Quencher 1). Non-Limiting Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: c. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and d. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. In methods wherein the probe comprises a signal-promoting molecule which is a fluorophore or a quencher, the method of detecting is one wherein the step of detecting the detectable signal comprises detecting fluorescence emission produced by the fluorophore of the probe. Signal-Promoting Molecule — Polypeptide Having Enzymatic Activity A signal-promoting molecule may be a polypeptide which has enzymatic activity. A non-limiting exemplary embodiment of such a polypeptide is horseradish peroxidase (HRP) which is described below. It will be appreciated that any other suitable alternative polypeptide which has enzymatic activity may also be used, simply by adapting the principles of probe structure described herein, and the discussion below concerning HRP applies mutatis mutandis to any other suitable alternative polypeptide. Horseradish Peroxidase (HRP) Horseradish peroxidase (HRP) is ~44KDa glycoprotein enzyme which is used extensively as a labelling and detection molecule in biochemical, molecular biological and immunochemical applications. HRP catalyzes the oxidation of a number of organic substrates by hydrogen peroxide. The HRP enzyme may have the following amino acid sequence (SEQ ID NO: 5): MHHHHHHHSGSGSGAQLTPTFYDNSCPNVSNIVRDTIVNELRSDPRIAASILRLHF HDCFVNGCDASILLDNTTSFRTEKDAFGNANSARGFPVIDRMKAAVESACPRTVS CADLLTIAAQQSVTLAGGPSWRVPLGRRDSLQAFLDLANANLPAPFFTLPQLKDSF RNVGLNRSSDLVALSGGHTFGKNQCRFIMDRLYNFSNTGLPDPTLNTTYLQTLRG LCPLNGNLS ALVDFDLRTPTIFDNKYYVNLEEQKGLIQSDQELF S SPNATDTIPLVR SFANSTQTFFNAFVEAMDRMGNITPLTGTQGQIRLNCRVVNSNSLLHDMVEVVDF VSSM. HRP Positioning In such a repressible cleavage-dependent signalling system, the nucleotide position(s) on the oligonucleotide(s) at which HRP is tethered are not critical, provided that at least one linker attaching HRP comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that at least one linker attaching HRP to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, HRP is tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, HRP may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is HRP, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Non-Limiting Exemplary Probe Embodiments A detection probe of the invention may be a probe wherein the signal-promoting molecule is a polypeptide, and wherein when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal may be produced in a reaction which is dependent upon the polypeptide. A detection probe of the invention may be a probe wherein the polypeptide has enzymatic activity, and the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the polypeptide. A detection probe of the invention may be a probe wherein the polypeptide is a horseradish peroxidase (HRP) enzyme. A detection probe of the invention may be a probe wherein the polypeptide is a horseradish peroxidase (HRP) enzyme which has the following amino acid sequence (SEQ ID NO: 5): MHHHHHHHSGSGSGAQLTPTFYDNSCPNVSNIVRDTIVNELRSDPRIAASIL RLHFHDCFVNGCDASILLDNTTSFRTEKDAFGNANSARGFPVIDRMKAAVESACP RTVSCADLLTIAAQQSVTLAGGPSWRVPLGRRDSLQAFLDLANANLPAPFFTLPQL KD SFRN VGLNRS SDL VAL S GGHTFGKNQCRFIMDRL YNF SNTGLPDPTLNTT YLQ TLRGLCPLNGNLSALVDFDLRTPTIFDNKYYVNLEEQKGLIQSDQELFSSPNATDTI PLVRSFANSTQTFFNAFVEAMDRMGNITPLTGTQGQIRLNCRVVNSNSLLHDMVE VVDFVSSM. The detection probe may be a probe having the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, L is the linker, and HRP is an HRP enzyme which has the following amino acid sequence (SEQ ID NO: 5; in the direction N-terminal to C-terminal): MHHHHHHHSGSGSGAQLTPTFYDNSCPNVSNIVRDTIVNELRSDPRIAASIL RLHFHDCFVNGCDASILLDNTTSFRTEKDAFGNANSARGFPVIDRMKAAVESACP RTVSCADLLTIAAQQSVTLAGGPSWRVPLGRRDSLQAFLDLANANLPAPFFTLPQL KDSFRNVGLNRSSDLVALSGGHTFGKNQCRFIMDRLYNFSNTGLPDPTLNTTYLQ TLRGLCPLNGNLSALVDFDLRTPTIFDNKYYVNLEEQKGLIQSDQELFSSPNATDTI PLVRSF ANSTQTFFNAF VEAMDRMGNITPLTGTQGQIRLNCRVVNSNSLLHDMVE VVDFVSSM. In such a probe L may be attached to HRP at any suitable amino acid position of HRP, such as at the terminal amino acid position at the N-terminal end of HRP, at the terminal amino acid position at the C-terminal end of HRP, or at any other amino acid position, including any one or more K residues and any one or more C residues. Non-Limiting Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. The method is one wherein the detectible signal is produced in a reaction in a solution which is dependent upon the enzymatic activity of HRP of the probe, the method comprising detecting the activity of the HRP enzyme (HRP holoenzyme) in the solution. The method may be a method wherein the step of detecting the activity of HRP holoenzyme in the solution comprises reacting HRP holoenzyme in the solution with an oxidase and a substrate for the oxidase, and detecting the presence of a product produced by the reaction. The method may be a method wherein the step of detecting the activity of HRP holoenzyme in the solution comprises: A. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase, p-hydroxybenzoic acid and 4-aminoantipyrine; or b) p-hydroxybenzoic acid, 4-aminoantipyrine and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 504 nm; or B. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase and 3,3',5,5'-tetramethybenzidine (TMB); or b) 3,3',5,5'-tetramethybenzidine (TMB) and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 450 nm or 650 nm; or C. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase and 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS); or b) 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 405 nm. Signal-Promoting Molecule — Component of an Enzyme Complex, a Domain of an Enzyme, a Fragment of an Enzyme or an Enzyme Cofactor A signal-promoting molecule may be a polypeptide which is a component of an enzyme complex, a domain of an enzyme, a fragment of an enzyme or an enzyme cofactor. A non-limiting exemplary embodiment of such a polypeptide is beta-galactosidase alpha peptide (alpha peptide) which is described below. It will be appreciated that any other suitable alternative polypeptide which is a component of an enzyme complex, a domain of an enzyme, a fragment of an enzyme or an enzyme cofactor may also be used, simply by adapting the principles of probe structure described herein, and the discussion below concerning alpha peptide applies mutatis mutandis to any other suitable alternative polypeptide. Alpha Peptide The enzyme beta-galactosidase can be separated into two inactive fragments of different sizes, which on their own are incapable of hydrolysing a beta-galactosidase substrate. The smaller fragment is referred to as the alpha peptide, alpha fragment, alpha domain or enzyme donor, and these terms are used herein interchangeably. The alpha peptide is about 100 amino residues in length. The larger fragment is referred to as the omega peptide, omega fragment, omega domain, or enzyme acceptor, and these terms are used herein interchangeably. The omega fragment is about 900 amino residues in length. When the alpha and omega fragments are combined, the beta-galactosidase enzyme is reconstituted and is active. Active beta-galactosidase can then be detected. Alpha Peptide Positionins In such a repressible cleavage-dependent signalling system, the nucleotide position(s) on the oligonucleotide(s) at which alpha peptide is tethered are not critical, provided that at least one linker attaching alpha peptide comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that at least one linker attaching alpha peptide to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, alpha peptide is tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, alpha peptide may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is alpha peptide, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Non-Limiting Exemplary Probe Embodiments The detection probe may be a probe as described and defined further herein, wherein the signal-promoting molecule is a polypeptide which is a component of an enzyme complex, a domain of an enzyme, a fragment of an enzyme or an enzyme cofactor, and the detectible signal is produced in a reaction which is dependent upon the polypeptide. The detection probe may be a probe wherein the polypeptide is a beta-galactosidase alpha peptide. The detection probe may be a probe wherein the polypeptide is a beta-galactosidase alpha peptide having an amino acid sequence as set forth in any one of SEQ ID NOS: 6 to 56 as listed in the table below. The table provides a list of beta-galactosidase alpha peptide amino acid sequences that can be used as signal-promoting molecules. Preferably the first linker is attached to the first amino acid residue of the sequence at the N-terminal end of the polypeptide (underlined, typically via (but not limited to) the addition of an azide on the N-terminus i.e. coupling of azidoacetic acid) and the second linker is attached to the second (underlined) amino acid residue of the sequence in the direction proximal to the C-terminal end. Preferably, the N-terminal amine of the peptide is reacted with azidoacetic acid to add the azide to the N-terminus. Alternative methods may involve the reaction of longer carbon chains or PEG based linkers. Further alternative methods may involve the reaction of bromo / iodo acetic acid with the N-terminus to conjugate the peptide with a oligo-SH. Peptide No. Alpha Peptide Amino Acid Sequence (N-terminal to C terminal) SEQ ID NO. 1 MTMITDSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEK SEQ ID NO: 6 2 MTMITDSLAVVLKRRDWENPGVTQLNRLAAHPPF ASWRNSE SEQ ID NO: 7 3 MTMITD SL A V VLQRRDKENPG VT QLNRL A AHPPF ASWRNSE SEQ ID NO: 8 4 MTMITDSLAVVLQRRDWKNPGVTQLNRLAAHPPF ASWRNSE SEQ ID NO: 9 5 MTMITDSLAVVLQRRDWEKPGVTQLNRLAAHPPF ASWRNSE SEQ ID NO: 10 6 MTMITDSLAVVLQRRDWENPGVTKLNRLAAHPPF ASWRNSE SEQ ID NO: 11 7 MTMITD SL A VVLQRRDWENPGVTQLKRLAAHPPF ASWRNSE SEQ ID NO: 12 8 MTMITD SLA VVLQRRDWENPGVTQLNRL A AHPPF ASKRNSE SEQ ID NO: 13 9 MTMITD SLA VVLQRRDWENPGVTQLNRL A AHPPF ASWRKSE SEQ ID NO: 14 10 SLAVVLQRRDWENPGVTQLNRLAAHPPFASWRNS EEARTDRPSQQLRSLNK SEQ ID NO: 15 11 SLAVVLQRRDWENPGVTQLNRLAAHPPFASWRNS EEARTDRPSQQLRSLNGEWRFAK SEQ ID NO: 16 12 SLAVVLQRRDWENPGVTQLNRLAAHPPFASWRNS EEARTDRPSQQLRSLNGEWRFAWFPAPEAVPEK SEQ ID NO: 17 13 VVLQRRDWENPGVTQLNRLAAHPPFASWRNSEEA RTDRPSQQLRSLNGEWRFAWFPAK SEQ ID NO: 18 14 ITDSLAVVLQRRDWENPGVTQLNRLAAHPPFASW RNSEEARTDRPSQQLRSLNGEWK SEQ ID NO: 19 15 SLAVVLQRRDWENPGVTQLNRLAAHPPFASWRNS EEARTDRPSQQLRSLNGEWRFAWFPAK SEQ ID NO: 20 16 SLAVVLQRRDWENPGVTQLNRLAAHPPFASWRNS EEARTDRPSQK SEQ ID NO: 21 17 MTMITDSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNK SEQ ID NO: 22 18 MTMITDSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAK SEQ ID NO: 23 19 MTMITDSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAWFPAPE AVPEK SEQ ID NO: 24 20 LQRRDWENPGVTQLNRLAAHPPFASWRNSEEART DRPSQQLRK SEQ ID NO: 25 21 VVLQRRDWENPGVTQLNRLAAIIPPrASWRNSEEA RTDRPSQQK SEQ ID NO: 26 22 RRDWENPGVTQLNRLAAHPPFASWRNSEEARTDR PSQQLRSLNK SEQ ID NO: 27 23 MTMITDSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEC SEQ ID NO: 28 24 MTMITDSLAVVLCRRDWENPGVTQLNRLAAHPPF ASWRNSE SEQ ID NO: 29 25 MTMITDSLAVVLQRRDCENPGVTQLNRLAAHPPFA SWRNSE SEQ ID NO: 30 26 MTMITDSLAVVLQRRDWCNPGVTQLNRLAAHPPF ASWRNSE SEQ ID NO: 31 27 MTMITDSLAVVLQRRDWECPGVTQLNRLAAHPPF ASWRNSE SEQ ID NO: 32 28 MTMITDSLA VVLQRRDWENPGVTCLNRLAAHPPF ASWRNSE SEQ ID NO: 33 29 MTMITD SL A VVLQRRD WE N PG VT QLCRL A AH P P F ASWRNSE SEQ ID NO: 34 30 MTMITD SLA VVLQRRD WENPGVTQLNRL A AHPPF ASCRNSE SEQ ID NO: 35 31 MTMITD SLA VVLQRRD WENPGVTQLNRL A AHPPF ASWRCSE SEQ ID NO: 36 32 SLA VVLQRRD WENPGVTQLNRL AAHPPFASWRNS EEARTDRPSQQLRSLNC SEQ ID NO: 37 33 SLA VVLQRRD WENPGVTQLNRL AAHPPFASWRNS EEARTDRPSQQLRSLNGEWRFAC SEQ ID NO: 38 34 SLA VVLQRRD WENPGVTQLNRL AAHPPFASWRNS EEARTDRPSQQLRSLNGEWRFAWFPAPEAVPEC SEQ ID NO: 39 35 VVLQRRD WENPGVTQLNRL AAHPPFASWRNSEEA RTDRPSQQLRSLNGEWRFAWFPAC SEQ ID NO: 40 36 ITDSLA VVLQRRD WENPGVTQLNRL AAHPPFASW RNSEEARTDRPSQQLRSLNGEWC SEQ ID NO: 41 37 SLA VVLQRRD WENPGVTQLNRL AAHPPFASWRNS EEARTDRPSQQLRSLNGEWRFAWFPAC SEQ ID NO: 42 38 SLA VVLQRRD WENPGVTQLNRL AAHPPFASWRNS EEARTDRPSQC SEQ ID NO: 43 39 MTMITD SLA VVLQRRD WENPGVTQLNRL A AHPPF ASWRNSEEARTDRPSQQLRSLNC SEQ ID NO: 44 40 MTMITDSLA VVLQRRD WENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAC SEQ ID NO: 45 41 MTMITDSLA VVLQRRD WENPGVTQLNRL A AHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAWFPAPE AVPEC SEQ ID NO: 46 42 LQRRDWENPGVTQLNRLAAHPPFASWRNSEEART DRPSQQLRC SEQ ID NO: 47 43 WLQRRDWENPGVTQLNRLAAHPPFASWRNSEEA RTDRPSQQC SEQ ID NO: 48 44 RRDWENPGVTQLNRLAAHPPFASWRNSEE ARTDR PSQQLRSLNC SEQ ID NO: 49 45 GSSGSGSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNK SEQ ID NO: 50 46 GSSGSGSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAK SEQ ID NO: 51 47 GSSGSGSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAWFPAPE AVPEK SEQ ID NO: 52 48 GSSGSGSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAWFPAK SEQ ID NO: 53 49 GS SGSG SL AVVLQRRDWENPG VTQLNRL A AHPPF ASWRNSEEARTDRPSQK SEQ ID NO: 54 50 GSSGSGSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAK SEQ ID NO: 55 51 GSSGSGSLAVVLQRRDWENPGVTQLNRLAAHPPF ASWRNSEEARTDRPSQQLRSLNGEWRFAWFPAPE AVPEK SEQ ID NO: 56 The detection probe may be a probe having the structure: L2 wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; LI is the first linker; L2 is the second linker; and SEQ ID NO: X is any one of SEQ ID NOS 6 to 56, wherein in each sequence the underlined K residue or the underlined C residue is attached to LI and the other underlined residue is attached to L2, or wherein in each sequence the underlined K residue or the underlined C residue is attached to L2 and the other underlined residue is attached to LI. The detection probe may be a probe having the structure: L2 wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; LI is the first linker; L2 is the second linker; n is the number of nucleotide positions relative to the 3’ end of the probe; and SEQ ID NO: X is any one of SEQ ID NOS 6 to 56, wherein in each sequence the underlined K residue or the underlined C residue is attached to LI and the other underlined residue is attached to L2, or wherein in each sequence the underlined K residue or the underlined C residue is attached to L2 and the other underlined residue is attached to LI. The detection probe may be a probe having the structure: 5'^cHgwucl eotide—o wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide; LI is the first linker; L2 is the second linker; n is the number of nucleotide positions relative to the 3’ end of the probe; and SEQ ID NO: X is any one of SEQ ID NOS 6 to 56, wherein in each sequence the underlined K residue or the underlined C residue is attached to LI and the other underlined residue is attached to L2, or wherein in each sequence the underlined K residue or the underlined C residue is attached to L2 and the other underlined residue is attached to LI. The detection probe may be a probe having the structure: wherein * is the terminal phosphate group at the 5’ end of the oligonucleotide; ** is the terminal phosphate group at the 3’ end of the oligonucleotide; LI is the first linker; L2 is the second linker; and SEQ ID NO: X is any one of SEQ ID NOS 6 to 56, wherein in each sequence the underlined K residue or the underlined C residue is attached to LI and the other underlined residue is attached to L2, or wherein in each sequence the underlined K residue or the underlined C residue is attached to L2 and the other underlined residue is attached to LI. The detection probe may be a probe having the structure: 12 q 3' * q 5*-ohgonucteotide 14* S'-oHgonucieotide 2-3* wherein * is the terminal phosphate group at the 3’ end of the first oligonucleotide; ** is the terminal phosphate group at the 3’ end of the second oligonucleotide; LI is the first linker; L2 is the second linker; and SEQ ID NO: X is any one of SEQ ID NOS 6 to 56, wherein in each sequence the underlined K residue or the underlined C residue is attached to LI and the other underlined residue is attached to L2, or wherein in each sequence the underlined K residue or the underlined C residue is attached to L2 and the other underlined residue is attached to LI. The detection probe may be a probe having any one of the following 32 structures, wherein in each structure: * is the terminal phosphate group at the 3’ end of the oligonucleotide; LI is the first linker; and L2 is the second linker: structure 8: structure 10: structure 12: structure 24: structure 26: structure 32: Non-Limitins Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. The method is one wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the enzyme or enzyme complex comprising the component, the enzymatic activity of the enzyme comprising the domain, the enzymatic activity of the enzyme comprising the fragment, the enzymatic activity of the enzyme comprising the cofactor. The method may be one wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of beta-galactosidase mediated by the beta-galactosidase alpha peptide of the probe. The method may be one wherein the step of detecting the detectible signal comprises: 1) contacting the beta-galactosidase alpha peptide of the probe in solution with betagalactosidase omega fragment (omega peptide) to form beta-galactosidase holoenzyme; and 2) detecting the presence of beta-galactosidase holoenzyme in solution. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: a colorimetric assay, a fluorescence assay, a chemiluminescence assay, a bioluminescence assay or an electrochemical assay. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with orthonitrophenyl-P-D-galactopyranoside (ONPG) in solution, thereby forming a chromophore reaction product ortho-nitrophenol (ONP), and B. detecting the presence of ortho-nitrophenol (ONP), optionally by measuring the absorbance of the solution at 420 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with chlorophenol red-P-D-galactopyranoside (CPRG) in solution, thereby forming a chromophore reaction product chlorophenol red; and B. detecting the presence of chlorophenol red, optionally by measuring the absorbance of the solution at 570 to 595 nm, e.g. 575 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-bromo-4-chloro-3-indolyl-P-D-galactopyranoside in solution, thereby forming a blue precipitate reaction product 5,5'-dibromo-4,4'-dichloro-indigo; and B. detecting the presence of 5,5'-dibromo-4,4'-dichloro-indigo. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-Bromo-3-indolyl P-D-galactopyranoside in solution, thereby forming a blue precipitate reaction product 5,5'-dibromo-indigo; and B. detecting the presence of 5,5'-dibromo-indigo. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-Bromo-6-chl oro-3-indolyl-P-D-galactopyranoside in solution, thereby forming a magenta precipitate reaction product 5,5' dibromo-6,6'-dichloro-indigo; and B. detecting the presence of 5,5' dibromo-6,6'-dichloro-indigo, optionally by measuring the absorbance of the solution at 565 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 6-Chloro-3-indolyl-beta-D-galactopyranoside in solution, optionally together with nitroblue tetrazolium salt (NBT), thereby forming a precipitate reaction product 6,6' dichloro indigo; and B. detecting the presence of 6,6' dichloro indigo. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 3,4-Cyclohexenoesculetin p-D-galactopyranoside in the presence of Fe3 in solution, thereby forming a black precipitate reaction product, which is a complex formed of 2 molecules of 3,4-Cyclohexenoesculetin (2,3-dihydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one) and one Fe3+; and B. detecting the presence of the black precipitate reaction product. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 5-Iodo-3-indolyl-P-D-galactopyranoside in solution, thereby forming a purple precipitate reaction product 5,5'-diiodo indigo; and B. detecting the presence of 5,5'-diiodo indigo, optionally by immunoblotting, or by measuring the absorbance of the solution at 575 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 1 -Methyl-3-indolyl-P-D-galactopyranoside in solution, thereby forming a green precipitate reaction product l,l'-dimethyl isoindigo; and B. detecting the presence of l,T-dimethyl isoindigo. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 6-O-p-galactopyranosyl-luciferin in solution in the presence of luciferase, preferably firefly luciferase; and B. detecting the emission of light (luminescence), preferably by measuring emission at 560 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 3-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenoxy-beta-galactopyranoside (Galacton Star) or 2-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenoxy-beta-galactopyranoside (Galacton plus) in solution; and B. detecting the production of 3-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenolate or 2-chloro-5-5-chloro-4'-methoxyspiro[adamantane-2,3'-[l,2]dioxetan]-4'-yl)phenolate moiety by detecting chemiluminescence. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 7-(P-D-galactopyranosyloxy)-3h-phenoxazin-3-one (resorufin P-D-galactopyranoside) in solution, thereby releasing 7-hydroxy-3H-phenoxazin-3-one (resorufin); and B. detecting the presence of resorufin, optionally by measuring the fluorescence emission of the solution at 580 nm upon excitation at 570 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-Methylumbelliferyl-P-D-galactopyranoside (4-Methylumbelliferyl-P-D-galactoside; MUG) in solution, thereby releasing 4-methylumbelliferone (4-MU); and B. detecting the presence of 4-MU, optionally by measuring the fluorescence emission of the solution at 445 nm upon excitation at 372 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with fluorescein di(P-D-galactopyranoside) (FDG) in solution, thereby releasing fluorescein; and B. detecting the presence of fluorescein, optionally by measuring the fluorescence emission of the solution at 517-519 nm upon excitation at 495-498 nm. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-amynophenyl-beta-D-galactopyranoside (ANPG) to form 4-aminophenol; B. oxidising 4-aminophenol at an electrode, the electrode comprising or consisting of a conductive material, such as carbon, graphite, graphene, gold, platinum, or conductive metal oxides, and measuring the current through the electrode; and C. detecting a change in the current, whereby an increase in the current correlates with an increase in the rate of formation of 4-aminophenol. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-Methoxyphenyl-P-d-galactopyranoside (MPGP) to produce 4-methoxyphenol; B. detecting 4-methoxyphenol at an electrode by an electrochemical detection method, optionally by voltammetry or by amperometry, the electrode comprising or consisting of a conductive material, such as carbon, graphite, graphene, gold, platinum, or conductive metal oxides, and measuring the current through the electrode; and C. detecting a change in the voltage or current, whereby an increase in the voltage or current correlates with an increase in the rate of formation of 4-methoxyphenol. The method may be one wherein the step of detecting the presence of betagalactosidase holoenzyme in solution comprises: A. reacting beta-galactosidase holoenzyme with 4-Methoxyphenyl-P-d-galactopyranoside (MPGP) in the presence of an oxidase, preferably tyrosinase, to form 4-methoxycatechol; B. detecting 4-methoxycatechol at an electrode by an electrochemical detection method, optionally by voltammetry or by amperometry, by oxidising 4-methoxycatechol at an electrode, the electrode comprising or consisting of a conductive material, such as carbon, graphite, graphene, gold, platinum, or conductive metal oxides, and measuring the current through the electrode; and C. detecting a change in the voltage or current, whereby an increase in the voltage or current correlates with an increase in the rate of oxidation of 4-methoxycatechol. Signal-Promoting Molecule — Activator of an Enzyme or an Activator of an Enzyme Complex A signal-promoting molecule may be a polypeptide which is an activator of an enzyme or an activator of an enzyme complex. Such a polypeptide has the capability of stimulating the activity of another molecule, such as an enzyme or enzyme complex. A non-limiting exemplary embodiment of such a polypeptide is Ml3 polypeptide which is described below. It will be appreciated that any other suitable alternative polypeptide which is an activator of an enzyme or an activator of an enzyme complex may also be used, simply by adapting the principles of probe structure described herein, and the discussion below concerning M13 peptide applies mutatis mutandis to any other suitable alternative polypeptide. Ml 3 Polypeptide M13 is a peptide that corresponds with the CaM-binding domain of calmodulin (CaM), a Ca2+ binding protein. The CaM-binding domain mediates the interaction between calmodulin and small-conductance Ca2 -activated K channels (SK channels). M13 polypeptide may also be referred to as M13 peptide, and these terms are used interchangeably herein. Ml 3 Polypeptide Positioning In such a repressible cleavage-dependent signalling system, the nucleotide position(s) on the oligonucleotide(s) at which Ml 3 polypeptide is tethered are not critical, provided that at least one linker attaching Ml3 polypeptide comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that at least one linker attaching M13 polypeptide to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, Ml3 polypeptide is tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, M13 polypeptide may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is M13 polypeptide, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 and SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Non-Limiting Exemplary Probe Embodiments The detection probe may be a probe as described and defined further herein, wherein the polypeptide is an activator of an enzyme or an activator of an enzyme complex, and the detectible signal is produced in a reaction which is dependent upon the polypeptide. The detection probe may be a probe wherein the polypeptide is M13 polypeptide. The detection probe may be a probe wherein the polypeptide is M13 polypeptide having any one of the amino acid sequences as set forth in the table below. Peptide No. M13 Polypeptide Amino Acid Sequence (N-terminal to C terminal) SEQ ID NO. 1 KRRWKKNFIAVS AANRFKKIS S SGAL SEQ ID NO: 57 2 KRRWKKNFIAVS AANRFKKIS S SGALK SEQ ID NO: 58 3 KRRWKKNFIAVS AANRFKKIS S SGALC SEQ ID NO: 59 The table provides a list of M13 peptide amino acid sequences that can be used as signal-promoting molecules. Preferably the first linker is attached to the first amino acid residue of the sequence at the N-terminal end of the polypeptide (underlined, typically via (but not limited to) the addition of an azide on the N-terminus i.e. coupling of azidoacetic acid). If a second linker is used, the second linker is preferably attached to the second (underlined) amino acid residue of the sequence in the direction proximal to the C-terminal end. Preferably, the N-terminal amine of the peptide is reacted with azidoacetic acid to add the azide to the N-terminus. Alternative methods may involve the reaction of longer carbon chains or PEG based linkers. Further alternative methods may involve the reaction of bromo / iodo acetic acid with the N-terminus to conjugate the peptide with a oligo-SH. The detection probe may be a probe having the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. Non-Limitins Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. The method is one wherein the detectible signal is produced in a reaction which is dependent upon activation of the enzyme or enzyme or activation of the enzyme complex by the polypeptide of the probe. The method may be one wherein the detectible signal is produced in a reaction which is dependent upon activation of the enzyme or activation of the enzyme complex by the Ml 3 polypeptide of the probe. The method may be one wherein the detectible signal is produced in a reaction comprising: A. contacting the M13 polypeptide of the probe with SUMOl / sentrin specific peptidase 1 (SENP1) in the presence of a SUMO-alpha peptide fusion protein, whereupon SENP1 catalyses the cleavage of the SUMO-alpha peptide fusion protein to release free beta-galactosidase alpha peptide, and B. detecting the presence of free beta-galactosidase alpha peptide. In such a method the step of detecting the presence of free alpha peptide may comprise: 1) contacting the beta-galactosidase alpha peptide of the probe in solution with betagalactosidase omega fragment (omega peptide) to form beta-galactosidase holoenzyme; and 2) detecting the presence of beta-galactosidase holoenzyme in solution. In any of these methods, the step of detecting the presence of beta-galactosidase holoenzyme in solution may comprise: a colorimetric assay, a fluorescence assay, a chemiluminescence assay, a bioluminescence assay or an electrochemical assay. In any of these methods, the step of detecting the presence of beta-galactosidase holoenzyme in solution may comprise any one of the colorimetric assays, fluorescence assays, chemiluminescence assays, bioluminescence assays or electrochemical assays described above in the sub-section “Non-Limiting Exemplary Detection Embodiments” of the section “Sign al-Promoting Molecule - Component of an Enzyme Complex, a Domain of an Enzyme, a Fragment of an Enzyme or an Enzyme Cofactor”. Sisnal-Promotins Molecule — Small Molecule Which can Promote the Formation of a Molecular Complex, Such as A Protein:Protein Complex. A signal-promoting molecule may be a small molecule which can promote the formation of a complex between two or more further molecules, such as the formation of a protein:protein complex, including a dimeric protein:protein complex. Non-limiting exemplary embodiments of such a small molecule are everolimus and rapamycin which are described below. It will be appreciated that any other suitable alternative small molecules which can promote the formation of a complex between two or more further molecules, such as the formation of a protein:protein complex, including a dimeric protein:protein complex may also be used, simply by adapting the principles of probe structure described herein, and the discussion below concerning everolimus and rapamycin applies mutatis mutandis to any other suitable alternative small molecules. Everolimus and Rapamycin Everolimus and rapamycin are inhibitors or mammalian target of rapamycin (mTOR) kinase. Everolimus is derivative of rapamycin. Rapamycin and everolimus bind to FKBP12 (FK 506-binding protein of 12 kDa) to prevent mTOR from activating mTORCl. Everolimus and Rapamycin Positioning In such a repressible cleavage-dependent signalling system, the nucleotide position(s) on the oligonucleotide(s) at which everolimus and rapamycin are tethered are not critical, provided that at least one linker attaching everolimus and rapamycin comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that at least one linker attaching everolimus and rapamycin to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, everolimus and rapamycin are tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, everolimus and rapamycin may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is everolimus and rapamycin, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 and SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Non-Limitins Exemplary Probe Embodiments The detection probe may be a probe as described and defined further herein, wherein the small molecule promotes the formation of a molecular complex, such as a protein:protein complex, and the detectible signal is produced in a reaction which is dependent upon the formation of the molecular complex or protein:protein complex. The detection probe may be a probe wherein the small molecule is everolimus, which has the structure: The detection probe may be a probe which has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. The detection probe may be a probe wherein the small molecule is rapamycin, which has the structure: The detection probe may be a probe which has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. Non-Limitins Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. The method is one wherein the detectible signal is produced in a reaction which is dependent upon the formation of a molecular complex, such as a protein:protein complex, mediated by the small molecule of the probe. The method may be one wherein: A. the probe is any one of the above-described probes wherein the signal promoting molecule is everolimus, and wherein the detectible signal is produced in a reaction which is dependent upon the formation of a protein:protein complex mediated by the everolimus small molecule of the probe; or B. the probe is any one of the above-described probes wherein the signal promoting molecule is rapamycin, and wherein the detectible signal is produced in a reaction which is dependent upon the formation of a protein:protein complex mediated by the rapamycin small molecule of the probe. The method may be one wherein the step of detecting the detectible signal comprises: A. contacting the everolimus or rapamycin of the probe with FK506 binding protein (FKBP) and FKBP-rapamycin-binding (FRB) domain in solution, whereby everolimus or rapamycin causes the dimerization of FKBP and FBR, and B. detecting the presence of the FKBP-FBR dimer in the solution. The method may be one wherein the step of detecting the presence of the FKBP-FBR dimer comprises: C. providing a circular-permutated nano-luc fusion protein comprising (in sequential order in the direction N-terminal to C-terminal): i. FKBP, preferably having the amino acid sequence GVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPF KFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIP PHATLVFDVELLKLE (SEQ ID NO: 60); and ii. a first linker, preferably having the amino acid sequence GGSGGSGG (SEQ ID NO: 61); and iii. a C-terminal portion of nano-luc, preferably having the amino acid sequence VTGWRLCERILA (SEQ ID NO: 62); and iv. a second linker, preferably having the amino acid sequence GGSGSGSGSGGSGSGGS (SEQ ID NO: 63); and v. the remaining (N-terminal) portion of nano-luc, preferably having the amino acid sequence DNMVFTLEDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPI QRIVLSGENGLKIDIHVIIPYEGLSGDQMGQIEKIFKVVYPVDDHHFK VILHYGTLVIDGVTPNMIDYFGRPYEGIAVFDGKKITVTGTLWNGN KIIDERLINPDGSLLFRVTING (SEQ ID NO: 64); and vi. a third linker, preferably having the amino acid sequence SGSGSGG (SEQ ID NO: 65); and vii. FBR, preferably having the amino acid sequence LWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTL KETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVF RRIS (SEQ ID NO: 66); optionally wherein the fusion protein has an affinity tag at the N-terminal end of the protein before the FKBP sequence, preferably a six-histidine tag immediately before the FKBP sequence; and wherein nano-luc is the ATP independent 19.1 kDa catalytically-active subunit of the luciferase enzyme of Oplophorus gracilirostris\ D. contacting the everolimus or rapamycin of the probe with the fusion protein in the presence of 2-furanylmethyl-deoxy-coelenterazine (furimazine) or 6-(4-Hydroxyphenyl)-2-[(4-hydroxyphenyl)methyl]-8-(phenylmethyl)-7H-imidazo[l,2-a]pyrazin-3-one (coelenterazine); and E. detecting the emission of light (luminescence), optionally by measuring emission at 460 nm. An exemplary full-length circular-permutated nano-luc fusion protein amino acid sequence is shown below (SEQ ID NO: 67): MDHHHHHHGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRD RNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHAT LVFDVELLKLEGGSGGSGGVTGWRLCERILAGGSGSGSGSGGSGSGGSDNMVFTL EDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPIQRIVLSGENGLKIDIHVI IPYEGLSGDQMGQIEKIFKVVYPVDDHHFKVILHYGTLVIDGVTPNMIDYFGRPYE GIAVFDGKKITVTGTLWNGNKIIDERLINPDGSLLFRVTINGSGSGSGGLWHEMWH EGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQ EWCRKYMKSGNVKDLTQ AWDLYYHVFRRIS. Signal-Promoting Molecule — Small Molecule Which Promotes the Activation of an Enzyme or an Enzyme Complex A signal-promoting molecule may be a small molecule which promotes the activation of an enzyme or an enzyme complex. A non-limiting exemplary embodiment of such a small molecule is methotrexate which is described below. It will be appreciated that any other suitable alternative small molecule which promotes the activation of an enzyme or an enzyme complex may also be used, simply by adapting the principles of probe structure described herein, and the discussion below concerning methotrexate applies mutatis mutandis to any other suitable alternative small molecule. Methotrexate Methotrexate is a small molecule pharmaceutical agent commonly used in chemotherapy and as an immune-system suppressant. Methotrexate Positioning In such a repressible cleavage-dependent signalling system, the nucleotide position(s) on the oligonucleotide(s) at which methotrexate is tethered are not critical, provided that at least one linker attaching methotrexate comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that at least one linker attaching methotrexate to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, methotrexate is tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, methotrexate may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is methotrexate, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease ITT, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 and SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Non-Limiting Exemplary Probe Embodiments The detection probe may be any one of the probes as described and defined further herein, wherein the small molecule promotes the activation of an enzyme or an enzyme complex, and the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex. The detection probe may be any one of the probes as described and defined further herein, wherein the signal-promoting molecule is methotrexate, having the structure: The detection probe may be a probe which has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. Non-Limiting Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. The method is one wherein the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex mediated by the small molecule of the probe. The method may be one wherein the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex mediated by the methotrexate small molecule of the probe. The method may be one wherein the step of detecting the detectible signal comprises: A. contacting the methotrexate (MTX) of the probe with a binding partner to form a protein binding partner:MTX complex; and B. detecting the presence of the complex. The method may be one wherein the step of detecting the detectible signal comprises: C. contacting the MTX of the probe with a fusion protein comprising glucose dehydrogenase (GDH) and a calmodulin domain (CaM-GDH) together with the protein binding partner (CaM-GDH-protein binding partner); and D. measuring GDH activity. Such a method may be one wherein: A. the methotrexate:protein binding partner complex comprises a dihydrofolate reductase:MTX complex and the step detecting the complex comprises contacting the cleaved MTX with a CaM-GDH-dihydrofolate reductase fusion protein, and measuring GDH activity; B. the methotrexate:protein binding partner complex comprises a thymidylate synthase:MTX complex and the step detecting the complex comprises contacting the cleaved MTX with a CaM-GDH-thymidylate synthase fusion protein, and measuring GDH activity; or C. the methotrexate:protein binding partner complex comprises an anti-methotrexate VHH antibody:MTX complex and the step detecting the complex comprises contacting the cleaved MTX with a CaM-GDH-anti-methotrexate VHH antibody fusion protein, and measuring GDH activity, optionally wherein GDH activity is measured via a colorimetric assay or via an electrochemical assay. Signal-Promoting Molecule — Small Molecule Which is a Cofactor of an Enzyme or an Enzyme Complex A signal-promoting molecule may be a small molecule which is a cofactor of an enzyme or an enzyme complex. A non-limiting exemplary embodiment of such a small molecule is hemin which is described below. It will be appreciated that any other suitable alternative small molecule which is a cofactor of an enzyme or an enzyme complex may also be used, including any suitable substituted hemin, simply by adapting the principles of probe structure described herein, and the discussion below concerning hemin applies mutatis mutandis to any other suitable alternative small molecule. Hemin Hemin is a cofactor for horseradish peroxidase (HRP). When hemin is complexed with HRP apoenzyme, HRP holoenzyme is thereby produced. HRP holoenzyme is the active form of the HRP enzyme. HRP apoenzyme is inactive. Substituted hemins which act as cofactors for HRP have also been described. Hemin Positioning In such a repressible cleavage-dependent signalling system, the nucleotide position(s) on the oligonucleotide(s) at which hemin is tethered are not critical, provided that at least one linker attaching hemin comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. A user can readily structure a probe such that at least one linker attaching hemin to the oligonucleotide comprises a cleavage site which is cleaved, by the action of a cleavage molecule having phosphatase / exonuclease activity, when the probe is in double-stranded form and hybridised to the target sequence of interest in a test solution comprising a RPA-SSB, and conversely such that cleavage by the cleavage molecule does not occur when the probe is in single-stranded form and not hybridised to the target sequence of interest in a test solution comprising a RPA-SSB. These criteria can readily be tested empirically according to methods described herein. Preferably, hemin is tethered to the oligonucleotide(s) via at least one linker which is attached to the terminal phosphate group at the 3’ terminal end of the probe. Accordingly, this linker comprises the cleavage site which includes the terminal phosphate group, and cleavage is thereby effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity. Alternatively, hemin may be tethered to the oligonucleotide(s) via at least one linker which is attached to another chemical group and / or at another nucleotide position of the oligonucleotide(s), provided that the probe is structurally arranged such that cleavage at the cleavage site is effected by the action of a cleavage molecule which is any molecule having phosphatase / exonuclease activity and the probe is suitable for use in an RPA reaction. In any of the probes described and defined herein where the signal promoting molecule is hemin, the cleavage molecule is any molecule having phosphatase / exonuclease activity, preferably Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 and SEQ ID NO: 4. The probe is structured such that cleavage at the cleavage site is dependent upon cleavage by the cleavage molecule by the action of its phosphatase / exonuclease activity and not by any apurinic / apyrimidinic (AP) endonuclease activity of a cleavage molecule. Non-Limitins Exemplary Probe Embodiments The detection probe may be any one of the probes as described and defined further herein, wherein the small molecule is a cofactor of an enzyme or an enzyme complex, and the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex. Such a detection probe may be a probe wherein the signal-promoting molecule is hemin, which has the structure: Such a detection probe may be a probe which has the structure: wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker. Non-Limitins Exemplary Detection Embodiments A method of detecting a target nucleic acid sequence of interest in a test solution may be a method comprising: A. providing a test solution comprising: a. a RPA single-stranded DNA-binding protein (SSB) molecule; b. a cleavage molecule; c. any one of the detection probes as described immediately above in the section “Non-Limiting Exemplary Probe embodiments”; and d. a sample suspected of comprising a target nucleic acid sequence of interest; and B. detecting a detectible signal produced by the signal-promoting molecule of the probe, upon: a. hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; and b. cleavage at the cleavage site of the probe by the cleavage molecule. The method may be one wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise: 1. a recombinase agent; 2. a recombinase loading protein; 3. a polymerase; and 4. forward and reverse nucleic acid primers for amplification. The method may be further defined according to the disclosure and description herein. The method may be one wherein the detectible signal is produced in a reaction which is dependent upon the conversion of an apoenzyme or apoenzyme complex into a holoenzyme or holoenzyme complex mediated by the small molecule cofactor of the probe. Such a method may be one wherein the detectible signal is produced in a reaction which is dependent upon the conversion of an apoenzyme or apoenzyme complex into a holoenzyme or holoenzyme complex mediated by the hemin small molecule of the probe. In any such method the detectible signal may be produced in a method comprising: A. contacting in a solution the hemin of the probe with horseradish peroxidase (HRP) apoenzyme, thereby forming HRP holoenzyme; and B. detecting the activity of HRP holoenzyme in the solution. In any such method the step of detecting the activity of HRP holoenzyme in the solution may comprise reacting HRP holoenzyme in the solution with an oxidase and a substrate for the oxidase, and detecting the presence of a product produced by the reaction. In any such method the step of detecting the activity of HRP holoenzyme in the solution may comprise: A. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase, p-hydroxybenzoic acid and 4-aminoantipyrine; or b) p-hydroxybenzoic acid, 4-aminoantipyrine and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 504 nm; or B. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase and 3,3',5,5'-tetramethybenzidine (TMB); or b) 3,3',5,5'-tetramethybenzidine (TMB) and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 450 nm or 650 nm; or C. (i) reacting HRP holoenzyme in the solution with: a) glucose, e.g. P-d-glucose, glucose oxidase and 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS); or b) 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) and H2O2, thereby forming a chromophore reaction product; and (ii) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 405 nm. Signal-Promoting Molecule Positioning As noted elsewhere herein in any repressible cleavage-dependent signalling system described and defined herein, the nucleotide position(s) on the oligonucleotide(s) at which the signal promoting molecule is tethered are not critical, provided that at least one linker attaching the signal promoting molecule comprises a cleavage site and the probe is capable of operating according to the RPA-SSB-mediated repressible / activatable mechanism of action described herein and is suitable for use in an RPA reaction. Accordingly, in the probes of the present invention the signal-promoting molecule is tethered to the oligonucleotide(s) via at least one linker which is attached to a chemical group of the oligonucleotide(s) and which thereby defines a cleavage site on the oligonucleotide, wherein the cleavage site is susceptible to cleavage mediated by phosphatase or exonuclease activity when contacted with a cleavage molecule having phosphatase or exonuclease activity. Conversely, in the probes of the present invention the signal-promoting molecule is tethered to the oligonucleotide(s) via at least one linker which is attached to a chemical group of the oligonucleotide(s) and which thereby defines a cleavage site on the oligonucleotide, wherein the cleavage site is not susceptible to cleavage mediated by apurinic / apyrimidinic (AP) endonuclease activity if contacted with a cleavage molecule having apurinic / apyrimidinic (AP) endonuclease activity. Preferably the at least one linker which defines the cleavage site and which tethers the signal-promoting molecule to the oligonucleotide(s) of the probe, is attached to the signal-promoting molecule and to the terminal phosphate group at the 3’ end of the oligonucleotide. Accordingly, the terminal phosphate group at the 3 ’ end of the probe comprises the cleavage site, and this terminal phosphate group is cleaved by the cleavage molecule via the phosphatase activity of the cleavage molecule. Alternatively, the at least one linker which defines the cleavage site and which tethers the signal-promoting molecule to the oligonucleotide(s) of the probe, is attached to the signal-promoting molecule and to the oligonucleotide at a position other than the terminal phosphate group at the 3’ end of the probe. Accordingly, the terminal phosphate group at the 3’ end of the probe does not comprise the cleavage site comprising the linker. In such an alternative probe structure, the terminal phosphate group at the 3’ end of the probe is susceptible to initial cleavage by the cleavage molecule via the phosphatase activity of the cleavage molecule. Subsequently, the cleavage molecule cleaves at the cleavage site comprising the linker via the exonuclease activity of the cleavage molecule. In a probe where the signal-promoting molecule is tethered to the oligonucleotide by only a single linker, the linker can be attached to any nucleotide position on the oligonucleotide, provided that the probe is structured to operate in the manner described above. Preferably, the linker which tethers the signal-promoting molecule to the oligonucleotide of the probe is attached to the signal-promoting molecule and to the terminal phosphate group at the 3’ end of the oligonucleotide. In a probe where the signal-promoting molecule is tethered to an oligonucleotide by two linkers, the probe may structured as described below. The probe may be one wherein: (i) a first linker is attached to a first position on the signal-promoting molecule and to a chemical group at nucleotide position n in the oligonucleotide, and (ii) a second linker is attached to a second position on the signalpromoting molecule and to a chemical group at nucleotide position n+x in the oligonucleotide wherein: A. the chemical group on the oligonucleotide to which the first linker is attached comprises the cleavage site, preferably a phosphate group; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal; and wherein the terminal nucleotide position at the 3’ end of the oligonucleotide is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 5’ end of the oligonucleotide are defined as n+x where x is an integer of 0 or more. The probe may be one wherein: (i) a first linker is attached to a first position on the signal-promoting molecule and to a chemical group at nucleotide position n+x in the oligonucleotide(s), and (ii) a second linker is attached to a second position on the signalpromoting molecule and to a chemical group at nucleotide position n+x+y in the oligonucleotide(s) wherein: A. the chemical group to which the first linker is attached comprises the cleavage site; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal; and wherein the terminal nucleotide position at the 3’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 5’ end of the oligonucleotide(s) are defined as n+x and n+x+y where x is an integer of 1 or more and y is an integer of 0 or more. In a probe where the signal-promoting molecule is tethered to the oligonucleotide by two linkers, the probe may alternatively be structured as described below. The probe may be one wherein: (i) a first linker is attached to a first position on the signal-promoting molecule and to a chemical group at nucleotide position n in the oligonucleotide(s), and (ii) a second linker is attached to a second position on the signalpromoting molecule and to a chemical group at nucleotide position n+x in the oligonucleotide(s) wherein: A. the chemical group on the oligonucleotide to which LI is attached comprises the cleavage site, optionally a phosphate group; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal; and wherein the terminal nucleotide position at the 5’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 3’ end of the oligonucleotide(s) are defined as n+x where x is an integer of 0 or more. The probe may be one wherein: (i) a first linker (LI) is attached to a first position on the signal-promoting molecule and to a chemical group at nucleotide position n+x in the oligonucleotide(s), and (ii) a second linker (L2) is attached to a second position on the signal-promoting molecule and to a chemical group at nucleotide position n+x+y in the oligonucleotide(s) wherein: A. the chemical group to which LI is attached comprises the cleavage site; and B. when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal; and wherein the terminal nucleotide position at the 5’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 3’ end of the oligonucleotide(s) are defined as n+x and n+x+y where x is an integer of 1 or more and y is an integer of 0 or more. Recombinase Polymerase Amplification (RPA) Recombinase polymerase amplification (RPA) is a method for isothermal amplification of nucleic acids. In general, in a first step of RPA, a recombinase agent is contacted with first and second nucleic acid primers and a recombinase loading protein to form first and second nucleoprotein primers. In general, in a second step, the first and second nucleoprotein primers are contacted with a double stranded template nucleic acid to form a first double stranded structure at a first portion of the first strand of the template nucleic acid, and a second double stranded structure at a second portion of the second strand of the template nucleic acid such that the 3’ ends of the first nucleic acid primer and the second nucleic acid primer are orientated towards each other on a given nucleic acid molecule. In general, in a third step, the 3’ end of the first and the second nucleoprotein primers are extended by polymerase to generate first and second double stranded nucleic acids, and first and second displaced single strands of nucleic acid. A single stranded stabilizing agent is employed to stabilize the first and second displaced single strands of nucleic acid. Generally, the second and third steps can be repeated until a desired degree of amplification is reached. RPA methods are disclosed extensively, e.g., in US Patent No. 7,270,981; US Patent No. 7,399,590; US Patent No. 7,666,598; US Patent No. 7,435,561 and International Patent Application Publication No. WO2010 / 141940. In addition, for a comprehensive recent review see: Review: a comprehensive summary of a decade development of the recombinase polymerase amplification, Li, J. et al., 2019, Analyst, 144, pp31-67). As explained below, certain RPA components may be attached / tethered / tagged to one or more IDR-polypeptides. An IDR-polypeptide comprises an intrinsically disordered region. IDR-polypeptides suitable for use in RPA reactions are described extensively in patent application publication WO 2021 / 094746A1. Recombinase Agent RPA methods use a recombinase agent. Any IDR-polypeptide may be attached / tethered / tagged to any recombinase agent. A recombinase agent is a molecule, typically an enzyme, that can coat a single stranded nucleic acid, typically DNA (ssDNA) to form a nucleoprotein filament. Such filaments can then “scan” a double stranded nucleic acid molecule, typically DNA (dsDNA) for regions of sequence homology / complementarity. When complementary sequences are located, the nucleoprotein filament (comprising the recombinase agent) strand invades the double stranded nucleic acid molecule creating a short hybrid and a displaced strand bubble known as a D-loop. Any suitable recombinase agent may be used in the RPA methods described herein, and may be tagged with any suitable IDR amino acid sequence. The recombinase agent may originate from a prokaryotic, eukaryotic or viral organism. The recombinase agent may be RecA, UvsX, RadA, RadB, Rad 51 or any functional variant, analog, homolog or derivative of any of these proteins. Any combination of these proteins may be used. Suitable recombinase agents include the E. colt RecA protein, the T4 UvsX protein, or any homologous protein or protein complex from any phyla. Eukaryotic RecA homologues are generally named Rad51 after the first member of this group to be identified. Other non-homologous recombinase agents may be utilized in place of RecA, for example RecT or RecO. Exemplary recombinase agents include RecA and UvsX, and fragments or mutants thereof and combinations thereof. The RecA and UvsX proteins can be obtained from any species. RecA and UvsX fragments or mutant proteins can also be produced using the available RecA and UvsS protein and nucleic acids sequences, and molecular biology techniques. Exemplary UvsX proteins include those derived from myoviridae phages, such as T4, T2, T6, Rb69, Aehl, KVP40, Acinetobacter phage 133, Aeromonas phage 65, cyanophage P-SSM2, cyanophage PSSM4, cyanophage S-PM2, Rbl4, Rb32, Aeromonas phage 25, Vibrio phage nt-1, phi-1, Rbl6, Rb43, Phage 31, phage 44RR2.81, Rb49, phage Rb3, and phage LZ2. Additional exemplary recombinase agents include archaebacterial RADA and RADB proteins and eukaryotic (e.g., plant, mammal, and fungal) Rad51 proteins (e.g, RAD51, RAD51B, RAD51C, RAD51D, DMC1, XRCC2, XRCC3, and rec A). The recombinase agent is preferably UvsX, T4 UvsX, T6 UvsX, RBI8 UvsX, E.coli phage wV7 UvsX, Shigella phage CB8 UvsX, Shigella phage Shfl2 UvsX, E.coli phage ARI UvsX, phage vB_EcoM_G4507 UvsX, Shigella phage SHFML-11 UvsX, Escherichia phage vBEcoM^D UvsX, E. coli RecA, E. coh RadA, E. coli RadB, E. coli Rad 51 or any functional variant, analog, homolog or derivative thereof or any combination thereof. A particularly preferred recombinase agent is Escherichia phage vBEcoMDalCa UvsX. The recombinase agent may also comprise a C-terminal deletion of acidic residues to improve its activity. Any functional variants, analogs, homologs or derivatives of the recombinase agent above may also function itself as a recombinase agent and these functional variants, analogs, homologs or derivatives are also contemplated as a recombinase agent to be used in the processes described and defined herein. For example, a small peptide from RecA, has been shown to retain some aspects of the recombination properties of RecA. This peptide comprises residues 193 to 212 of A. coli RecA and can mediate pairing of single stranded oligonucleotides. The recombinase agent (e.g., UvsX) may be a mutant or hybrid recombinase agent. Mutant forms of UvsX are described in U.S. Patent No. 8,071,308. The mutant UvsX may be an Rb69 UvsX that includes at least one mutation in the Rb69 UvsX amino acid sequence, wherein the mutation is selected from the group consisting of (a) an amino acid which is not histidine at position 64, a serine at position 64, the addition of one or more glutamic acid residues at the C-terminus, the addition of one or more aspartic acid residues at the C-terminus, and a combination thereof. The mutant UvsX may be a T6 UvsX having at least one mutation in the T6 UvsX amino acid sequence, wherein the mutation is selected from the group consisting of (a) an amino acid which is not histidine at position 66; (b) a serine at position 66; (c) the addition of one or more glutamic acid residues at the C-terminus; (d) the addition of one or more aspartic acid residues at the C-terminus; and (e) a combination thereof Where a hybrid recombinase agent is used, the hybrid protein may, for example, be a UvsX protein that includes at least one region that includes an amino acid sequence derived from a different UvsX species. The region may be, for example, the DNA-binding loop-2 region of UvsX. If desired, the recombinase agent may be a temperature-sensitive (referred to herein as "ts") recombinase agent. If a ts recombinase agent is used, the RPA reaction may be started at one temperature (the permissive temperature) and terminated at another temperature (the non-permissive temperature). Combinations of permissive temperatures may be, for example 25°C / 30°C, 30°C / 37°C, 37°C / 42°C and the like. The ts protein may be reversible. A reversible ts protein’s activity is restored when it is shifted from the non-permissive temperature to the permissive temperature. While any recombinase agent concentration may be used, preferred recombinase concentrations may be, for example, in the range of 0.2-12 pM, 6-12 pM, 4-12 pM and 4-6 pM, preferably about 5 pM, more preferably about 4.8 pM Recombinase agents generally require the presence of ATP, ATPyS, or other nucleoside triphosphates or their analogs. It is preferred that recombinase agents are used in a reaction environment in which regeneration of targeting sites can occur shortly following a round of D-loop stimulated synthesis. Completed recombination events involving recombinase disassembly will avoid a stalling of amplification or very inefficient linear amplification of ssDNA caused by oscillating single sided synthesis from one end to the other. Exemplary UvsX recombinase agents tagged with amino acid tag sequences comprising intrinsically disordered regions (IDRs) are set out in the table below. Name of protein SEQ ID NO. Amino acid sequence UvsX (7His) 68 MS1ADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEHHHHHHH UvsX-fib-1 69 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEPGFSPRGGGFGGRGGFG DRGGRGGRGGFGGGRGRGGGFRGRGRHHHHHHH UvsX-fib-2 70 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEPGFSPRGGGFGGRGGFG DRGGRGGRGGFGGGRGRGGVEHHHHHH UvsX-fib-3 71 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEPGFSPRGGGFGGRGGFG DRGGRGGRGGVEHHHHHH UvsX-fib-4 72 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDA1CLFYDSEFGITPAYLKSMGVDPERVIHTP1QSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNE1VEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEPGFSPRGGGFGGRGGVE HHHHHH UvsX- HNRNPA1 73 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEASASSSQRGRSGSGNFG GGRGGGFGGNDNFGRGGNFSGRGGFGGSRGGGGYGGSG DGYNGFGNDGSNFGGGGSYNDFGNYNNQSSNFGPMKGG NFGGRSSGPYGGGGQYFAKPQNQGGYGVSSSSSSYGSGRR FHHHHHHH UvsX-DDX 74 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEMGDEDWEAEINPHMSSY VPIFEKDRYSGENGDNFNRTPASSSEMDDGPSRRDHFMKS GFASGRNFGNRDAGECNKRDNTSTMGGFGVGKSFGNRGF SNSRFEDGDSSGFWRESSNDCEDNPTRNRGFSKRGGYRDG NNSEASGPYRRGGRGSFRGCRGGFGLGSPNNDLDPDECM QRTGGLFGSRRPVLSGTGNGDTSQSRSGSGSERGGYKGLN EEVITGSGKNSWKSEAEGGESSDTQHHHHHHH UvsX addPolCTD 75 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEHHHHHHHFEFSPFGAYG EAPTS PGFGVSSPGFSPTSPTYSPTSPAYSPTSPSYSPTSPSYS PTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTS PSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPAY SPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPT SPGY SPGSPAY SPKQDEQTAALEHHHHHH UvsX-fusPolII 76 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNETSPSYSPTSPSYSPTSPGY SPTSPAYSPTSPTYSPTSPTYSPHHHHHHH UvsX-PCFll 77 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEQVQMQLRQVFSQDQQV LQERMRYHELQQQQQQQYHETKDMVGSYTQNSNSAIPLF GNNSDTTNQQNSHHHHHHH UvsX-Sup 78 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEMSDSNQGNNQQNYQQY SQNGNQQQGNNRYQGYQAYNAQAQPAGGYYQNYQGYS GYQQGGYQQYQYNPQGGYQQYNPQGGYQQYNPQGGYQ QQFNPQGGRGNYKNFNYNNNLQGYQHHHHHHH UvsX-DoubleX 79 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNE HHHHHHHFEFEIVEAEVDELINSKVEKFKSPESKSKSAADL ETDLEQLSDMEEFNEIVEAEVDELINSKVEKFKSPESKSKSA ADLETDLEQLSDMEEFNHHHHHH Superpositive 80 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNRIVKAKVKRLINSKVKKFKSPK SKSKSAAKLKTKLKQLSKMKKFNKIVKAKVKKLINSKVRK CIZCDFCIZCIZC A ALT L'TIZl LfAI CVAAVt? r iSl.oe iSk1Sl.oiSk.o-iAk / A.lSkJL / lSk £ 1rTLJnLJnLrTLi^ Supemegative 81 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFR1VTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSEVEEFDSPES DSDEAADLETDLEQLSDMEEFNE1VEAEVDELINSEVEDFD SPESDSDEAADLETDLEQLSDMEEFNHHHHHHH UvsX His2 82 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGGIDPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEAGHHHHHPHAHHPLSQS SGHHHHHHHHHHQGYGGSG UvsX+PCF+His 2 83 MSIADLKSRLIKASTSKMTAELTTSKFFNEKDVIRTKIPMLN IAISGAIDGGMQSGLTIFAGPSKSFKSNMSLTMVAAYLNKY PDAICLFYDSEFGITPAYLKSMGVDPERVIHTPIQSVEQLKI DMVNQLETIERGEKVIVFIDSIGNMASKKETEDALNEKSVA DMTRAKSLKSLFRIVTPYFSIKNIPCVAVNHTIETIEMFSKT VMTGGTGVMYSADTVFIIGKRQIKDGSDLQGYQFVLNVEK SRTVKEKSKFFIDVKFDGG1DPYSGLLDMALELGFVVKPKN GWYAREFLDEETGEMIREEKSWRAKDTNCTTFWGPLFKH QPFRDAIKRAYQLGAIDSNEIVEAEVDELINSKVEKFKSPES KSKSAADLETDLEQLSDMEEFNEQVQMQLRQVFSQDQQV LQERMRYHELQQQQQQQYHETKDMVGSYTQNSNSAIPLF GNN SDTTNQQN S AGHHHHHPHAHHPLSQS SGHHHHHHHH Hn^UY CrCrSCr Recombinase Loadins Protein RPA methods may additionally include / use a recombinase loading protein. Any suitable recombinase loading protein may be used in the RPA methods described herein. The recombinase loading protein may originate from a prokaryotic, viral or eukaryotic organism. Exemplary recombinase loading proteins include E. coli RecO, E. coli RecR, UvsY, and mutants or fragments thereof, or combinations thereof. Exemplary UvsY proteins include those derived from myoviridae phages, such as T4, T2, T6, Rb69, Aehl, KVP40, Acinetobacter phage 133, Aeromonas phage 65, cyanophage P-SSM2, cyanophage PSSM4, cyanophage S-PM2, Rbl4, Rb32, Aeromonas phage 25, Vibrio phage nt-1, phi-1, Rbl6, Rb43, Phage 31, phage 44RR2.8t, Rb49, phage Rb3, and phage LZ2. Preferred recombinase loading proteins are UvsY, E. colt RecO, E. coli RecR or any functional variant, analoge, homologe or derivative of any of these proteins. A particularly preferred UvsY recombinase loading protein is Escherichia phage STO UvsY. Any combination of any of these proteins may be used. Preferred concentrations of these proteins is between 0.1-24 pM, 6-24 pM, 4-24 pM and 4-12 pM, preferably about 10 pM, more preferably about 8.6 pM. The recombinase loading protein may be present at between about 0.5 to about 2 times the micromolar concentration of the recombinase agent. Exemplary UvsY recombinase loading proteins tagged with amino acid tag sequences comprising intrinsically disordered regions are set out in the table below. Name of protein SEQ ID NO. Amino acid sequence UvsY [Phage STO] 84 MHHHHHHHMKLEDLQEELDADLAIDMSKLQYETANNVK LYSKWLRKHSFIRKEMLRIETQKKTALKARLDYYSGRGDG DEFSMDRYEKSEMKTVLAADKDVLKIETTLQYWGILLEFC SGALDAVKSRSFALKHIQDMREFEAGQ UvsY C-Pol CTD 85 MHHHHHHHHKLEDLQEELDADLAIDMSKLQYETANNVKL YSKWLRKHSFIRKEMLRIETQKKTALKARLDYYSGRGDGD EFSMDRYEKSEMKTVLAADKDVLKIETTLQYWGILLEFCS GALDAVKSRSFALKHIQDMREFEAGQSGSGSGPTSPSYSPT SPSYSPYSPAYS UvsY fib [short] 86 MHHHHHHHHKLEDLQEELDADLAIDMSKLQYETANNVKL YSKWLRKHSFIRKEMLRIETQKKTALKARLDYYSGRGDGD EFSMDRYEKSEMKTVLAADKDVLKIETTLQYWGILLEFCS GALDAVKSRSFALKHIQDMREFEAGQSGSGSGRGGGFGGR GGFGDRGGRGGRGGFGG UvsY Supl 87 MHHHHHHHHKLEDLQEELDADLAIDMSKLQYETANNVKL YSKWLRKHSFIRKEMLRIETQKKTALKARLDYYSGRGDGD EFSMDRYEKSEMKTVLAADKDVLKIETTLQYWGILLEFCS GALDAVKSRSFALKHIQDMREFEAGQSGSGYNPQGGYQQ NNL UvsY Supl HIS2 88 MAGHHHHHPHAHHPLSQSSGHHHHHHHHHHQGYGGSGK LEDLQEELDADLAIDMSKLQYETANNVKLYSKWLRKHSFI RKEMLRIETQKKTALKARLDYYSGRGDGDEFSMDRYEKS EMKTVLAADKDVLKIETTLQYWGILLEFCSGALDAVKSRS FALKHIQDMREFEAGQSGSGYNPQGGYQQNNLQ Single Strand Stabilizing Agent RPA methods use a single strand stabilizing agent. Any suitable single strand stabilizing agent (single stranded DNA binding protein) may be used. Optionally, any suitable IDR-polypeptide may be attached / tethered / tagged to any single strand stabilizing agent. A single strand stabilizing agent is used to stabilize nucleic acids during the various exchange reactions that occur during the RPA reaction. In particular a single strand stabilizing agent is used to stabilize recombinase / ssDNA nucleoprotein filaments. A single strand stabilizing agent can be derived or obtained from any species, e.g., from a prokaryotic, viral or eukaryotic species. Single strand stabilizing agents include single stranded DNA binding proteins from E. coli and those derived from myoviridae phages, such as T4, T2, T6, Rb69, Aehl, KVP40, Acinetobacter phage 133, Aeromonas phage 65, cyanophage P-SSM2, cyanophage PSSM4, cyanophage S-PM2, Rb 14, Rb32, Aeromonas phage 25, Vibrio phage nt-1, phi-1, Rbl6, Rb43, Phage 31, phage 44RR2.81, Rb49, phage Rb3, and phage LZ2. Additional examples of single strand stabilizing agents included, denitrificans Alide_2047, Burkholderia thailandensis BthaB_33951, Prevotellapollens HMPREF9144 0124, and eukaryotic single stranded DNA binding protein replication protein A. Preferred single strand stabilizing agents are selected from the group consisting of Gp32, E. coli SSB protein, phage T4 Gp32 protein, phage Rb69 Gp32, phage vBEcoMNBGl Gp32, and derivatives thereof and any combination thereof. Particularly preferred single strand stabilizing agents are Gp32 and in particular phage vBE^ Gp32. Any combination of any of these proteins may be used. One preferred concentration of the single strand stabilizing agent is between approximately 5-30 pM, such as approximately 8.6 pM, preferably between approximately 15-25 pM, more preferably approximately 20 pM. Exemplary Gp32 single strand stabilizing agents tagged with amino acid tag sequences comprising intrinsically disordered regions are set out in the table below. Name of protein SEQ ID NO. Amino acid sequence Gp32 (7His) from phage vB 89 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC SSTHGDYDSCPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLHHHHHHH Gp32Super +ve 90 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVAKKVASKLKFKKKMEA FSSAKTKKKFMSSSSSKKSKLKKLLAGLMEAFSSAKTKK KFMSSSSSKKSKLKKLLAGLHHHHHHH Gp32Super -ve 91 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAM1AVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADDVASDLDDFDDDME AF S S ADTEDDFMS S S S SDD SDLDDLLAGLME AF S SADTED DFMSSSSSDDSDLDDLLAGLHHHHHHH Gp32- TripleXtail 92 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADDVASEFEIVEAEVDE LINSKVEKFKSPESKSKSAADLETDLEQLSDMEEFNEIVEA EVDELINSKVEKFKSPESKSKSAADLETDLEQLSDMEEFN EIVEAEVDELINSKVEKFKSPESKSKSAADLETDLEQLSD MEEFNHHHHHH Gp32-fib 93 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLPGFSPRGGGFG GRGGFGDRGGRGGRGGFGGGRGRGGGFRGRGRHHHHH HH Gp32-PCF11 94 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLNEQVQMQLRQ VFSQDQQVLQERMRYHELQQQQQQQYHETKDMVGSYT QNSNSAIPLFGNNSDTTNQQNSHHHHHHH Gp32-Sup 95 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLMSDSNQGNNQ QNYQQYSQNGNQQQGNNRYQGYQAYNAQAQPAGGYY QNYQGYSGYQQGGYQQYQYNPQGGYQQYNPQGGYQQ YNPQGGYQQQFNPQGGRGNYKNFNYNNNLQGYQHHHH HHH Gp32-Supl 96 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC SSTHGDYDSCPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLYNPQGGYQQH HHHHHH Gp32-Sup2 97 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLYNPQGGYQQY NPQGGYQQHHHHHHH Gp32-Sup3 98 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC SSTHGDYDSCPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLYNPQGGYQQY NPQGGYQQYNPQGGYQQHHHHHHH Gp32-Sup4 99 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLYNPQGGYQQY NPQGGYQQYNPQGGYQQYNPQGGYQQHHHHHHH Gp32-DDX 100 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLHHHHHHHFEF MGDEDWEAEINPHMSSYVPIFEKDRYSGENGDNFNRTPA SSSEMDDGPSRRDHFMKSGFASGRNFGNRDAGECNKRD NTSTMGGFGVGKSFGNRGFSNSRFEDGDSSGFWRESSND CEDNPTRNRGFSKRGGYRDGNNSEASGPYRRGGRGSFRG CRGGFGLGSPNNDLDPDECMQRTGGLFGSRRPVLSGTGN GDTSQSRSGSGSERGGYKGLNEEVITGSGKNSWKSEAEG GES SDTQLEHHHHHH Gp32 PolCTD 101 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLHHHHHHHFEF SPFGAYGEAPTSPGFGVSSPGFSPTSPTYSPTSPAYSPTSPS YSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYS PTSPSY SPTSPSY SPTSPSY SPTSPSY SPTSPSY SPTSPSY SPT QPQVQPTQPA VQPTQPQVQPTQPQVQPTQPQVQPTQPQVQPTQP C5 jt Cz jl kU jt Ji Cz Jr i. v jl cj Jr jl Cz jt C5 jl jt jl jt Cz jl Cz Jr jl Cz jl C5 jl Cz jl jl Jr jl jt jl jt NYSPTSPSYSPTSPGYSPGSPAYSPKQDEQLEHHHHHH Gp32 HNRNPA1 102 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC SSTHGDYDSCPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLASASSSQRGRS GSGNFGGGRGGGFGGNDNFGRGGNFSGRGGFGGSRGGG GYGGSGDGYNGFGNDGSNFGGGGSYNDFGNYNNQSSNF GPMKGGNFGGRSSGPYGGGGQYFAKPQNQGGYGVSSSS S SYGSGRRFHHHHHHH Gp32HRPl 103 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLGGNNGGNNM NRRGGNFGNQGDFNQMYQNPMMGGYNPMMNPQAMTD YYQKMQEYYQQMQHHHHHHH Gp32 HRP2 104 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLGGNNGGNNM NRRGGNFGNQGDFNQMYQNPMMGGYNPMMNPQAMTD YYQKMQEYYQQMQGGNNGGNNMNRRGGNFGNQGDFN QMY QNPMMGGYNPMMNPQAMTDYY QKMQEYY QQMQ HHHHHHH Gp32HISl 105 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPN1DDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLPQQNALHHHH GNS SHHHHHHHHHHHHHGQQA GP32 HIS2 106 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLAGHHHHHPHA y j| I Q | C / AC C / "'I TT TT TT TT TT TT TT TT TT Q X'"' jlxttje ooovrriiTLriJTLriJTLririiTLri i \jvjoxj GP32 HIS3 107 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLAGHHHHHHHH LPHLPPPHLHHHHHPQHHLHPGSAAAVHPVQQH GP32 HIS4 108 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWY1ETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLNHHASHGHHN SHHPQHHHHHHHHHHHPPPPAPQPPPPPQQQQ GP32 HIS5 109 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLSGHHGAHHGA HHPAAAAAYEAFRGPGFAGGGGADDMGAGHHHGAHHA AHHHHAAHHHHHHHHHHGGAGHGGGAGHH Gp32 Mimic 1 110 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLYDPTSPSYDPT SPSYDPTSPSYDPTSPSYDPTSPSYDPTSPSYDPTSPSHHHH HHH Gp32 Mimic2 111 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWY1ETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLYSPTDPSYSPT DPSYSPTDPSYSPTDPSYSPTDPSYSPTDPSYSPTDPSHHH HHHH Gp32 short pol ctd 112 MFKRKSTADLAAQMAKLNGNKGFSSEDKGEWKLKLDA SGNGQAVIRFLPAKTDDALPFTILVNHGFKKNGKWYIETC S STHGDYDS CPVCQYISKNDLYNTNKTEYSQLKRKTSYW ANILVVKDPQAPDNEGKVFKYRFGKKIWDKINAMIAVDT EMGETPVDVTCPWEGANFVLKVKQVSGFSNYDESKFLN QSAIPNIDDESFQKELFEQMVDLSEMTSKDKFKSFEELNT KFNQVLGTAALGGAAAAAASVADKVASDLDDFDKDME AFSSAKTEDDFMSSSSSDDSDLDDLLAGLTSPSYSPTSPSY SPTSPGYSPTSPAYSPTSPTYSPTSPTYSPHHHHHHH Polymerase RPA methods use a polymerase. Any suitable polymerase may be used. Optionally, any suitable IDR-polypeptide may be attached / tethered / tagged to any suitable polymerase. For the synthesis or amplification of DNA, DNA polymerase are preferably used. One advantage of the RPA reaction is that there is no limit on the type of polymerase that can be used. For example, eukaryotic, prokaryotic and bacteriophage polymerases can be used. The DNA polymerase may be a eukaryotic polymerase. Examples of eukaryotic polymerases that may be used include pol-a, pol-P, pol-5, pol-s or any functional variant, analoge, homologe or derivative thereof and any combination thereof. The DNA polymerase may be a prokaryotic polymerase. Examples of prokaryotic polymerases that may be used include E. coli DNA, polymerase I Klenow fragment, E. coli DNA polymerase I, E. coli DNA polymerase II, E. coli DNA polymerase III, E. coli DNA polymerase IV, E. coli DNA polymerase V, Bacillus stearothennophilus polymerase I large fragment, Bacillus subtilis Pol I large fragment (Bsu polymerase), Listeria monocytogenes DNA polymerase I, Staphylococcus aureus DNA polymerase 1 (Sau) or any functional variant, analoge, homologe or derivative thereof and any combination thereof. The DNA polymerase may be a bacteriophage polymerase. Examples of bacteriophage polymerases that may be used in the methods described herein include Phi-29 DNA polymerase, T7 DNA polymerase, bacteriophage T4 gp43 DNA polymerase, or any functional variant, analoge, homologe or derivative thereof and any combination thereof. The DNA polymerase typically contains strand displacing properties. DNA polymerases can use the free 3’-hydroxyl of the invading strand to catalyze DNA synthesis by incorporation of new nucleotides. A number of polymerases can use the 3’-hydroxyl of the invading strand to catalyze synthesis and simultaneously displace the other strand as synthesis occurs. For example E. coli polymerase II or III can be used to extend invaded D-loops. In addition, E. coli polymerase V normally used in SOS-lesion-targeted mutations in E. coli can be used. All of these polymerases can be rendered highly processive through their interactions and co-operation with the P-dimer clamp, as well as single stranded DNA binding protein (SSB) and other components. Other polymerases from prokaryotes, viruses, and eukaryotes can also be used to extend the invading strand. Many DNA polymerases possess 3’-5’ exonuclease activity, and some also possess 5’-3’ exonuclease activity, which is undesirable in RPA reactions as it results in digestion of one DNA strand progressively as the polymerase moves forward, rather than displacement. The 3’-5’ exonuclease has potential advantages as well as its obvious disadvantages. On the one hand 3’-5’ exonuclease activity increases the fidelity of the replication reaction, and can also prevent stalling of polymerases at points of misincorporation. High fidelity amplification is desirable for many DNA applications. The 3’-5’ exonuclease activity may also be appropriate for amplification of larger DNA fragments where stalling due to misincorporation could inhibit effective amplification. Despite these clear advantages of 3’-5’ exonuclease activity there are some disadvantages. The free oligonucleotides can be subject to end-dependant degradation when polymerases possessing 3’-5’ exonuclease are employed. Reaction noise can be reduced by utilising polymerases lacking 3’-5’ exonuclease activity. This suggests mispriming may result from oligonucleotides that have been shortened by the 3’-5’ exonuclease activity of polymerases. Consequently 3’-5’ exonuclease editing activity, pyrophosphorylysis, or any other similar editing activity can be a source of noise. This can be suppressed to a large extent by using saturating amounts of relatively cooperative Gp32 protein with some polymerases such as the Klenow fragment. Nevertheless, polymerases for use in the methods described herein might be provided which lack 3’-5’ exonuclease activity. The DNA polymerase may be present at a concentration of between 10,000 units / ml to 10 units / ml, such as between 5000 units / ml to 500 units / ml. Accessory Agents RPA reactions may further utilize accessory agents. Optionally, any IDR-polypeptide may be attached / tethered / tagged to any accessory agent. These accessory agents include a single strand binding protein, a helicase, a topoisomerase, a resolvase and any combination thereof. Such agents may possess unwinding, relaxing, and resolving activities respectively on nucleic acids. The accessory agents may also include RuvA, RuvB, RuvC, RecG, PriA, PriB, PriC, DnaT, DnaB, DnaC, DnaG, DnaX clamp loader, polymerase core complex, DNA ligase and a sliding clamp and any combination thereof. The sliding clamp may be E. coli P-dimer sliding clamp, the eukaryotic PCNA sliding clamp, or the T4 sliding clamp gp45 and a combination thereof. The accessory agents may include, in addition, DNA Polymerase III holoenzyme complex consisting of P-Clamp, DnaX Clamp Loader, and the Polymerase Core Complex. These latter accessory agents would allow the performance of leading and lagging RPA. RPA reactions may be performed with one or more additional enzymes that can promote efficient disassembly of recombinase agent / dsDNA complexes after initiation of DNA synthesis. These enzymes include those that are capable of stimulating 3’ to 5’ disassembly and those capable of supporting 5’ to 3’ disassembly. Such additional enzymes include several polymerases that can displace RecA in the 3’ to 5’ direction and can stimulate 3’ to 5’ disassembly of recombinase agent / dsDNA complexes. These DNA polymerases include E. coli PolV and homologous polymerase of other species. Inclusion of E. coli PolV or any functional variant, analoge, homologe or derivative thereof may improve the amplification efficiency. Other enzymes include a class of enzymes called helicases that can be used to promote the disassembly of RecA from dsDNA. These promote disassembly in both the 5’ to 3’ and 3’ to 5’ directions. An ideal helicase complex for stimulating disassembly of RecA from intermediates consists of the E. coli proteins RuvA and RuvB. The RuvAB complex promotes branch migration, and dissociates the RecA protein, allowing RecA to be recycled. Incorporation of RuvAB into the RPA mixture can promote the dissociation of RecA from dsDNA following strand exchange and displacement, allowing renewed synthesis of the duplicated template from the same site. Additionally, the RuvAB complex can act in concert with RuvC, which finally cuts and resolves Holliday junctions. With RuvC added to the RPA reaction mixture, complicated structures such as Holliday junctions formed at invasion sites, can be resolved. Still other enzymes include the E. coli RecG protein. RecG can stimulate disassembly of branch structures. Other enzymes useful in an RPA reaction mixture are those that allow continual generation of RecA nucleoprotein filaments in the presence of ATP and the single strand stabilizing agent. Accordingly, RecO and RecR, and optionally RecF proteins may be used. Primers RPA methods employ polymerases to generate copies of template nucleic acid molecules. RPA methods, including those of the present invention, therefore use primers to initiate extension by polymerases. It is a necessity of most nucleic acid polymerases that incorporation requires a free 3’-hydroxyl moiety on the terminal sugar of a short stretch of double stranded nucleic acid adjacent to the site of new synthesis. This stretch of double stranded nucleic acid is typically formed on a template by a short oligonucleotide typically having a complementary sequence, called a primer, which serves as an initiation site for the polymerase synthesis reaction. In some cases a 3’ modification, such as a sulfydryl, may be utilized to prime the synthesis reaction. The primer nucleic acid, which is base-paired with the template and extended by the polymerase, can be RNA or DNA. Typically, for in vitro reactions the primer is supplied as a short, often chemically synthesized, single stranded DNA (or modified DNA or RNA), and is usually referred to as an oligonucleotide primer. The primer is often of a specific sequence, although random primers can also be used. The primer is targeted to complementary sequences by virtue of its specific basepairing capacity. Formation of hybrids between the oligonucleotide primer and target nucleic acid are typically formed by incubation of the two in solution under conditions of salt, pH, and temperature that allow spontaneous annealing. The primers used in RPA may have a single stranded region for hybridization to the target DNA in the presence of a recombinase agent. The single stranded region may be, for example, about 10 bases, about 15 bases, about 20 bases, about 25 bases, about 30 bases, about 40 bases, and about 50 bases. Even longer regions such as about 75 bases, about 100 bases, about 150 bases or more may in theory be used. The choice of single stranded regions will depend on the complexity of the starting nucleic acid so that for example, a human genome may require a longer primer while a plasmid may require a much shorter primer. A preferred primer length is between about 30 to about 50 bases. For example, between 30 to 45 bases, between 30 to 40 bases, between 30 to 35 bases, between 35 to 40 bases, between 40 to 45 bases, and between 45 to 50 bases. While the above-referenced primer lengths are indicated, a recombinase and / or single stranded binding protein with an optimum primer length of less than 30 bases is also possible and envisioned. The primers used in RPA are preferably DNA although PNA, and RNA are also suitable for use as primers. It is noted that in fact, in natural DNA replication, DNA polymerases elongate genomic DNA by extension from RNA primers. Primers may be synthesized according to standard techniques. Modified bases and / or linker backbone chemistries may be desirable and functional in some cases. Additionally oligonucleotides may be modified at their ends, either 5’ or 3’, with groups that serve various purposes e.g. fluorescent groups, quenchers, protecting (blocking) groups (reversible or not), magnetic tags, proteins etc. In some cases single stranded oligonucleotides may be used for strand invasion, in others only partly single stranded nucleic acids may be used, the 5’ stretch of sequence of an invading nucleic acid being already hybridized to an oligonucleotide. The primers may comprise a 5’ region that is not homologous to the target nucleic acid. It should be noted that amplification may be achieved even if the primers are not completely complementary to the target nucleic acid. The primers may be non-complementary by having additional sequences at their 5’ ends. These additional sequences may be, for example, the sequence for a restriction endonuclease recognition site or the sequence that is complementary to a sequencing primer. The restriction endonuclease recognition site may be useful for subsequent cleavage of the amplified sequence. The use of restriction endonuclease that cleaves nucleic acid outside the restriction endonuclease recognition site is also contemplated. The sequence that is complementary for a sequencing primer may allow rapid DNA sequencing of the amplified product using commercially available primers or commercially available sequencing apparatus. Software to design oligonucleotides for use in in vitro DNA synthesis reactions is well established, particularly for use in PCR. The considerations for the RPA method are similar and include the optimisation of the melting temperature of the oligonucleotide, avoidance of hairpin formation within an oligonucleotide and selection against complementarity with other oligonucleotides present in a given reaction. It is therefore important to design oligonucleotide primer pairs to avoid undesirable side reactions. Besides optimising oligonucleotide sequence design there are additional approaches to reduce or eliminate primer dimer formation. As noted elsewhere herein, reaction noise can be reduced by utilising polymerases lacking 3’-5’ exonuclease activity. This suggests mispriming may result from oligonucleotides that have been shortened by the 3’-5’ exonuclease activity of polymerases. Consequently 3’-5’ exonuclease editing activity, pyrophosphorylysis, or any other similar editing activity can be a source of noise. In addition to using polymerases lacking exonuclease activity and the removal of pyrophosphate with pyrophosphatase, use of synthetic oligonucleotides with a non- hydrolysable backbone at the ultimate and / or penultimate link may be beneficial to reduce reaction noise. Alternative backbones could be selected from the considerable range of chemistries available such as phosphorothiorate, morpholino, locked nucleic acid, or peptide nucleic acid. Reagents for use in RPA Reactions Reagents for use in RPA methods are outlined below. dNTPs dNTPs, for example dATP, dGTP, dCTP, and dTTP, and derivatives and analogs thereof, may be added to an RPA reaction. In leading and lagging strand RPA, ATP, GTP, CTP, and UTP may also be included for synthesis of RNA primers. In addition, ddNTPs (ddATP, ddTTP, ddGTP and ddGTP and derivatives and analogs thereof) may be used to generate fragment ladders. The dNTP may be used at a concentration of between 1 mM to 200 mM of each NTP species. A mixture of dNTP and ddNTP may be used with ddNTP concentrations at 1 / 100 to 1 / 1000 of that of the dNTP (1 mM to 200 mM). The RPA may be performed in the presence of ATP, a hydrolysable ATP analog, or another nucleoside triphosphate. The ATP analog may be, for example, dATP, ddATP, or another nucleoside triphosphate analog such as UTP. Reducing agents Reducing agents which may be used in the RPA reaction include DTT. The DTT concentration may be between 1 mM and 10 mM, preferably 1 mM. ATP ATP or an ATP analog may be used in the RPA reaction. The ATP or ATP analog may be any of ATP, ATP-y-S, ATP-p-S, ddATP or a combination thereof. A preferred ATP or ATP analog concentration is between 1 mM and 10 mM, preferably 2.5 mM. System for A TP regeneration Other components of the RPA reaction may include a system for ATP regeneration (i.e. a system to convert ADP to ATP). Such a system may be, for example, phosphocreatine and creatine kinase. An ATP regeneration system permits persistent recombination reactions, as recombinases have an extremely high rate of ATP hydrolysis when bound to nucleic acids. Tn particular, the UvsX protein has a hydrolysis rate 10-20 times higher than RecA and can consume 200 molecules of ATP per minute per monomer. A number of systems are available. The creatine kinase / phosphocreatine system is preferred. When UvsX is employed the AMP that is produced may be converted into ATP. Chicken myokinase may additionally be used, which converts a molecule of AMP and one of ATP to two molecules of ADP. ADP can then be converted to ATP using the creatine kinase / phosphocreatine system. Poor regeneration of ATP can reduce the reaction rate. In the RPA methods described herein phosphocreatine is preferably used at a concentration of between 15-25 mM, more preferably 20 mM. Creatine kinase is preferably used at a concentration of between about 0.25-5.0 pM, more preferably 1 pM. Multivalent metal cations The buffer solution in an RPA reaction preferably contains multivalent metal cations. The buffer may contain a functional equivalent of a multivalent metal cation. The buffer solution in an RPA reaction more preferably contains divalent metal cations. The buffer may contain a functional equivalent of a divalent metal cation. Any suitable multivalent or divalent metal cation or functional equivalent thereof may be used, either as a single agent or combination of agents. The specific multivalent or divalent metal cation or functional equivalent thereof which achieves optimal results in promoting / enhancing IDR-mediated phase separation in an RPA reaction, as well as the specific concentration of the multivalent / divalent metal cation used may depend upon the specific IDR polypeptide which is used. The optimal multivalent / divalent metal cation or functional equivalent thereof, and the optimal concentration thereof, can be established empirically using routine tests, including RPA reactions themselves and / or the phase separation assays which are described further herein. The divalent metal cation may be Mg2 , Mn2+, Ca2+, Co2+, Ni2+ or Cu2+. Any of these cations may be used as a single agent, or any combination of cations may be used. Preferably they are used as single agents. Preferred divalent metal cations are Mg2+, Mn: and Ca2+. A particularly preferred divalent metal cation is Mg2+. A preferred concentration range is from 30 to 40 mM, more preferably from 33 to 39 mM. The buffer may contain Mg2+ ions, preferably at the indicated concentrations. More preferably the buffer contains MgOAc at the indicated concentrations. The buffer may contain Ca2+ ions, preferably at the indicated concentrations. More preferably the buffer contains CaCh at the indicated concentrations. The buffer may contain Mn2+ ions, preferably at the indicated concentrations. More preferably the buffer contains MnCh at the indicated concentrations. Buffers The buffer solution in an RPA reaction may be a Tris-HCl buffer, a Tris-Acetate buffer, or a combination thereof. The buffers may be present at a concentration of between about 10 mM to about 100 mM. A preferred buffer is a Tris-HCl buffer used at a concentration of between about 20 mM to about 30 mM, most preferably 25 mM. The buffered pH may be between 6.5 to 9.0, preferably pH 8.3. The buffer may contain potassium acetate between about 5 mM to about 50 mM, preferably between about 10 mM to about 40 mM. Reaction components A preferred but non-limiting set of reaction components for an RPA reaction is as follows below. Tris HC1 pH 8.3 25 mM KOAc 7.5 mM DTT 1 mM ATP 2.5 mM Phosphocreatine 20 mM Creatine kinase 1 pM dNTPs 1 mM Gp32 20 pM UvsX 4.8 pM UvsY 8.6 pM S. aureus DNA polymerase 1 (Sau) 0.135 pM Or B. subtilis DNA polymerase 1 (Bsu) MgOAc 33 mM Forward primer 0.4 pM Reverse primer 0.4 pM RPA Reaction Conditions RPA reactions may be incubated for any suitable length of time. Any of the RPA reactions may be incubated for between 5 minutes and 16 hours or more, such as between 15 minutes and 3 hours or between 30 minutes and 2 hours. The incubation may be performed until a desired degree of amplification is achieved. The desired degree of amplification may be 10 fold, 100 fold, 1000 fold, 10,000 fold, 100,000 fold or 1,000,000 fold amplification. One benefit of RPA is that the reaction may be performed at reduced temperatures compared to techniques which require thermal cycling, such as PCR. A further advantage of RPA is that the temperature is not critical and precise control, while preferred, is not absolutely necessary. For example, in a field environment, it is sufficient to incubate the RPA reaction at room temperature, or close to body temperature (35°C to 38°C), for example by placing the sample in a body crevice. Furthermore, the RPA reaction may be performed without temperature induced melting of the template nucleic acid. Thus, any of the RPA reactions may be performed at any suitable temperature. The RPA reactions may be performed at less than 45°C. The RPA reactions may be performed at less than 40°C. The RPA reactions may be performed at less than 35°C. The RPA reactions may be performed at less than 30°C. The RPA reactions may be performed at between 20°C and 50°C, between 20°C and 40°C, such as between 20°C and 30°C. Freeze Drying of RPA Reaction Components One advantage of RPA reactions is that the reagents, with the possible exception of the crowding agent (if used) and buffer, may be freeze dried (i.e., lyophilized) before use. Freeze dried reagents offer the advantage of not requiring refrigeration to maintain activity. For example, a tube of RPA reagents may be stored at room temperature. This advantage is especially useful in field conditions where access to refrigeration is limited. RPA reagents may be freeze dried onto the bottom of a tube, or on a bead or any other suitable type of solid support. To perform an RPA reaction the freeze dried reagents are reconstituted in a buffer solution and with a crowding agent (if used), or simply a buffered solution or water, depending on the composition of the freeze-dried reagents. Then a target nucleic acid, or a sample suspected to contain a target nucleic acid is added. The reconstitution liquid may also contain the sample nucleic acid. The reconstituted reaction is incubated for a period of time and the amplified nucleic acid, if present, is detected. In any one of the RPA methods described herein, the reagents that can be freeze dried before use include, at least, the recombinase agent, the recombinase loading protein, the single strand stabilizing agent, the DNA polymerase, the dNTPs or the mixture of dNTPs and ddNTPs, the reducing agent, the ATP or ATP analog, primers and probe. Stabilizing agents such as trehalose sugar may be included in the freeze dried mixture, for example at 20 mM to 200 mM and most optimally 40 mM to 80 mM in the reconstituted reaction, in order to improve freeze-drying performance and shelf life. If desired, the freeze dried reagents may be stored for 1 day, 1 week, 1 month or 1 year or more before use. Biochemical reaction reagents, such as RPA reagents, may be freeze dried together with a crowding agent. However, complex inter-related issues may exist which may justify the omission of a crowding agent in a lyophilized mixture. For example, the user may experience difficulty in the effective rehydration of the freeze dried crowding agent, or the user may experience other detrimental effects, including the need for larger lyophilized pellets. Accordingly, there may be advantages in being able to exclude some or all of a crowding agent from freeze dried materials which include among other things reduction of pellet size, shorter cycle times, and easier rehydration. However this has the consequential disadvantage that a crowding agent, if used, would need to be added fresh prior to use after the biochemical reaction mixture was rehydrated and prepared for use. This could be problematic in certain situations, such as for point-of-care use or field use. An advantage of the IDR-based reagents of the present invention is that they would not be expected to exhibit the same drawbacks as crowding agents in a lyophilized setting, and could therefore readily be freeze dried with other biochemical reaction components, thus obviating the need to add fresh additional reagents prior to use. Kits Comprising RPA Reaction Components Kits for performing an RPA reaction are also provided. A kit may comprise any of the reagents described herein for RPA in any one of the concentrations described above, including the detection probes described herein. The kit may comprise any of the IDR-tagged macromolecules and / or IDR-tagged polypeptides described and defined herein. Preferably the kit may further comprise additional RPA components selected from an RPA recombinase agent, and / or an RPA recombinase loading protein, and / or polymerase, and / or first and second nucleic acid primers, and / or a buffer, and / or a source of multivalent metal ions, preferably divalent metal cations such as Mg2+, Mn2 , Ca2 \ Co2 or \i2 . The reagents of the kit may be freeze dried, in which case the reagents may be provided in any suitable amount such that when reconstituted the appropriate reagent concentration is achieved. Other General Definitions DNA As used herein, the term “DNA” refers to deoxyribonucleic acid and derivatives thereof, the molecule that carries most of the genetic instructions used in the development, functioning and reproduction of all known living organisms and many viruses. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are known as polynucleotides and are composed of simpler units called deoxynucleotides. Each deoxynucleotide is composed of a nitrogencontaining nucleobase - cytosine (C), guanine (G), adenine (A), or thymine (T) - as well as a monosaccharide sugar called deoxyribose and a phosphate group. The deoxyribonucleotides are joined to one another in a chain by covalent (phosphodiester) bonds between the sugar of one deoxyribonucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. According to base pairing rules (A with T, and C with G), hydrogen bonds bind the nitrogenous bases of the two separate polynucleotide strands to make double-stranded DNA. The specific order of the monomers, i.e. the order of the deoxyribonucleotide bases linked to the sugar / phosphate-backbone, is called the DNA-sequence. RNA As used herein, the term “RNA” refers to ribonucleic acid and derivatives thereof. RNA is typically a single-stranded nucleic acid molecule, and is a polynucleotide composed of simpler units called ribonucleotides. Each ribonucleotide is composed of a nitrogen-containing nucleobase - cytosine (C), guanine (G), adenine (A), or thymine (T) -as well as a monosaccharide sugar called deoxyribose and a phosphate group. The ribonucleotides are joined to one another in a chain by covalent (phosphodiester) bonds between the sugar of one ribonucleotide and the phosphate of the next. The specific order of the monomers, i.e. the order of the ribonucleotide bases linked to the sugar / phosphate-backbone, is called the RNA-sequence. Amino Acid As used herein, the term “amino acid” refers to any natural or synthetic amino acid, that is, an organic compound comprising carbon, hydrogen, oxygen and nitrogen atoms, and comprising both amino (-NH2) and carboxylic acid (-COOH) functional groups. Typically, the amino acid is an a-, P-, y- or 6-amino acid. The amino acid may be one of the twenty-two naturally occurring proteinogenic a-amino acids. Alternatively, the amino acid may be a synthetic amino acid selected from a-Amino-n-butyric acid, Norvaline, Norleucine, Alloisoleucine, t-leucine, a-Amino-n-heptanoic acid, Pipecolic acid, a,P-diaminopropionic acid, aj-diaminobutyric acid, Ornithine, Allothreonine, Homocysteine, Homoserine, P-Alanine, P-Amino-n-butyric acid, P-Aminoisobutyric acid, y-Aminobutyric acid, a-Aminoisobutyric acid, isovaline, Sarcosine, N-ethyl glycine, N-propyl glycine, N-isopropyl glycine, N-methyl alanine, N-ethyl alanine, N-methyl P-alanine, N-ethyl P-alanine, isoserine, a-hydroxy-y-aminobutyric acid, Homonorleucine, O-methyl-homoserine, O-ethyl-homoserine, selenohomocysteine, selenomethionine, selenoethionine, Carb oxy glutamic acid, Hydroxyproline, Hypusine, Pyroglutamic acid, aminoisobutyric acid, dehydroalanine, P-alanine, y-Aminobutyric acid, 5-Aminolevulinic acid, 4-Aminobenzoic acid, citrulline, 2,3-diaminopropanoic acid, 3-aminopropanoic acid, hydroxytryptophan, selenohomocysteine, a-aminoglycine and diaminoacetic acid, 2,3-diaminopropionic acid, a,y-diaminobutyric acid, amino-2-keto-butyric acid, 4-acetylphenylalanine and formylglycine, azidolysine, azidoornithine, azidonorleucine, azidoalanine, azidohomoalanine, 4-azidophenylalanine and 4-azidomethylphenylalanine, homoallylglycine, 4-ethynylphenylalanine, 4-propargyloxyphenylalanine, propargylglycine, 4-(2-propynyl)proline, 2-amino-6-({[(lR,8S)-bicyclo[6.1.0]non-4-yn-9-ylmethoxy]carbonyl}amino)hexanoic acid and homopropargylglycine. An amino acid which possess a stereogenic centre may be present as a single enantiomer or as a mixture of enantiomers (e.g. a racemic mixture). The conventional one-letter or three-letter code for amino acid residues is used herein. Peptide and Polypeptide As used herein, the terms “peptide” and “polypeptide” are used interchangeably and refer to a biological molecule comprising polymers of amino acid monomers. Protein Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule (DNA, RNA, etc.), or to complex macromolecular assemblies. Enzyme The term “enzyme” refers to a protein or polypeptide having catalytic activity and having the capability of catalyzing a chemical reaction. Small molecule As used herein, the term “small molecule” refers to a low molecular weight chemical compound which has a known biological or pharmacological effect. Typically, a small molecule has Mw less than or equal to about 5 kDa. Optionally, the small molecule has Mw less than or equal to about 1.5 kDa, or less than or equal to about 1.0 kDa. Preferably, the small molecule has Mw less than or equal to about 900 Da. Small molecules make up the vast majority of pharmaceutical drugs and include biological molecules such as fatty acids, glucose, amino acids, cholesterol and secondary metabolites such as lipids, glycosides, alkaloids, and natural phenols. In contrary small molecules do not include e.g. polysaccharides, proteins and nucleic acids. Fluoroyhore The term “fluorophore” refers to chromophore or dye which is capable of fluorescence, i.e. a functional group and / or a molecule containing such a functional group which will absorb energy of a specific wavelength and re-emit energy at a different wavelength. Quencher The term “quencher” as used herein, generally refers to dye that is capable of reducing the emission of fluorescence of another dye, i.e. by absorbing the energy emitted by the other dye. Tether The term “tether” as used herein typically refers to the association between the signal-promoting molecule and an oligonucleotide of the probe. In all of the specific detection probe embodiments, the signal-promoting molecule is associated with an oligonucleotide of the probe via a linker, and therefore the association between the signal promoting molecule and the oligonucleotide is indirect, wherein the signal-promoting molecule is not itself directly chemically bonded to the oligonucleotide. Attach The term “attach” or “attached” as used herein typically refers to the association between the linker and the oligonucleotide of the probe or between the linker and the signal-promoting molecule. The associations between the linker and the oligonucleotide and between the linker and the signal-promoting molecule are direct, wherein the linker is directly chemically bonded to the oligonucleotide or signal-promoting molecule. Miscellaneous It is to be understood that the specific detection probes and detection methods described and defined herein are exemplary and non-limiting and may be adapted or tailored to the specific needs of the user. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to be limiting. As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, references to an entity such as “a molecule”, “a polypeptide” and so on, includes two or more such entities. Terms such as “about” and “approximately” are to be understood as encompassing the relevant figure + / - 10% of the value of the figure, or +1- 5% of the value of the figure unless the content clearly dictates otherwise. Where a range of numbers is presented as being “between” a lower value and an upper value, the range is to be interpreted as including the upper and lower values. For example, a range of between 22 mM to 50 mM, or between about 22 mM to about 50 mM, should be interpreted as including the values of 22 mM and 50 mM or the values of about 22 mM and about 50 mM. EXAMPLES The following Examples are provided to illustrate the invention but not to limit the invention. Example 1. Detection of RPA Products Using Doubly-Modified Probes -Fluorescence Detection. Purpose and summary of experiment This experiment was performed to demonstrate the cloaking by Gp32 of a probe, doubly modified at the 3’ terminal end with a fluorophore and a quencher. In one mode, the fluorophore remains attached to the 3’ terminal end of the probe while the quencher is released (see Figure 2A). In the other mode, the fluorophore is released while the quencher remains attached to the 3’ terminal end of the probe (see Figure 3 A). This example demonstrates that in the absence of mRPA-based DNA amplification the fluorophore or quencher is protected from phosphodiesterase attack by Exonuclease III (Exo III), and therefore the fluorophore remains quenched. Following the addition of template to a reaction, DNA amplification was initiated. During the reaction, the probe was incorporated into double stranded DNA as increasing amounts of DNA were synthesized. When the probe becomes hybridized to its target, thus forming a double stranded structure, Gp32, which is predominately a single stranded DNA binding protein, loses affinity for the probe and detaches. Gp32 removal from the probe leads the probe to become “uncloaked”, i.e. exposing the 3’ terminal end of the probe to Exo III attack. The phosphodiesterase activity of Exo III separates the fluorophore from the quencher. In both modes the increase in double stranded DNA amplification can be detected by an increase in fluorescent signal. Materials and methods RNA detection reactions specific for Sars Cov 2 (Wuhan-Hu-1 strain -MN908947.3) (COVID 0RF1 AB; Figure 2) or Egene (Figure 3) were set up by mixing 25 mM Tris HC1 pH 8.3, 7.5 mM KOAc, 1 mM DTT, 2.5 mM ATP, 20 mM phosphocreatine, 1 pM creatine kinase, 1 mM dNTPs, 0.4 pM forward primer, 0.4 pM reverse primer, 0.12 pM probe, 20 pM Gp32 fusion, 4.8 pM UvsX, 8.6 pM UvsY, 0.135 pM .S', aureus DNA polymerase, 0.326 pM RNA polymerase and 0.27 pM Exonuclease TIT. Reactions were initiated by the addition of template at the given concentration and with 28 mM MgOAc. The relevant primers and probe are indicated below. ORF1 AB (Figure 2B): Forward primer: 5 ’ -ACCGT AGCTGGTGTCTCTATCTGTAGT ACTATGAC-3 ’ (SEQIDNO: 113) Reverse primer: 5 ’ -TGCC AACC ACC AT AGAATTTGCTTGTTCC AATTAC-3 ’ (SEQ ID NO: 114) Probe: 5-CCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCAT C A A A A ATTA[dT-BHQ 1 ]-3 ’ [FAM-C7], (SEQIDNO: 115) where FAM is 6-fluorescein, and BHQ1 is Black Hole Quencherl. The target locus to which the probe binds is shown in Figure 2B (SEQ ID NO: 116). E gene (Figure 3B): Forward primer: 5’-GGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGC-3’ (SEQIDNO: 117) Reverse primer: 5 ’ -CGCAC AC AATCGAAGCGCAGTAAGGATGGCTAGTG-3 ’ (SEQIDNO: 118) Probe: 5 ’ -GGT ACGTT AATAGTT AAT AGCGTACTTCTTTTTCTTGC[dT-BHQ 1 ]TT-3 ’ [FAM-07] (SEQIDNO: 119) where FAM is 6-fluorescein, and BHQ1 is Black Hole Quencherl. The target locus to which the probe binds is shown in Figure 3B (SEQ ID NO: 120). Reactions were then incubated at 39 °C and placed in a fluorometer with magnetic mixing using a bearing ball. Results and conclusion Two different doubly-modified probe arrangements were tested. The results show that the single-stranded binding protein Gp32 sterically hinders Exonuclease III from accessing the 3’-end of the probe, i.e. Gp32 “cloaks” the probe. Once amplification progresses and the probe is incorporated into duplex DNA, Gp32 is released from the probe (i.e. the probe is “uncloaked”) and Exonuclease III can access and process the 3’end of the probe. In this example, a fluorophore was separated from a quencher allowing for the rapid detection of amplification of two example targets. In one mode, the fluorophore remains bound to the probe while the quencher is released (see Figure 2A-C), while in the other mode the fluorophore is released while the quencher remains attached to the probe (see Figure 3 A-C). Example 2. Detection of RPA Products Using an Oligo-HRP Probe Mediated by TDP-1 Processing - Colorimetric Detection. Purpose and summary of experiment This experiment was designed to test if tyrosyl-DNA phosphodiesterase 1 (TDP-1) nucleosidase was able to hydrolyze the 3’-phosphate of a probe oligonucleotide specifically in the presence of mRPA-derived target amplicon and to demonstrate colorimetric detection. TDP-1 processes 3’ ends from abnormal appendages. The natural substrate of this enzyme is principally phosphotyrosine linkages left by aberrant topoisomerase activity. The amino acid sequence of yeast (Saccharomyces cerevisiae) TDP-1 (yTDP-1) is provided below: MSRETNFNGTKRKRSDVAEKVAQRWKSVRYSAEMENMAPVNSNNDSDDCVIVSESKIIDL TNQEQDLSERIGTNDTAKGAVFKLMKSDFYEREDFMGEVEDMITLKDIFGTETLKRSILF S FQYELDFLLRQFHQNVENITIVGQKGTIMPIEARAMDATLAVILKKVKLIEITMPPFAS HHTKLIINFYDNGECKIFLPSNNFTSMETNLPQQVCWCSPLLKIGKEGLPVPFKRSLIEY LNSYHLKDIDELITKSVEEVNFAPLSELEFVYSTPSKFQSSGLLSFYNKLEKLSAGTSAS DTAKHYLCQTSSIGTSLSRARDENLWTHLMIPLFTGIMSPPAKDTAGRKKAEILPTNSLI NEYSQRKIKPYIIFPTEQEFVTSPLKWSSSGWFHFQYLQKKSYYEMLRNKFKVFYKQDPA MVTRRRGTTPAHSKFYMHCATNSTGPCDASQVFKELEWCLYTSANLSQTAWGTVSRKPRN YEAGVLYHSRRLANTRKVTCRTFTRDRRGCAGNPTHVAVPFTLPVIPYDLAEDECFCLAR HEND (SEQ ID NO: 3) The yTDP-1 enzyme used in the present example was expressed as a fusion protein comprising a maltose binding protein (MBP) domain and a N-terminal histidine tag to facilitate purification. The amino acid sequence of this fusion construct is provided below (yTDP-1 residues are underlined): MGHHHHHHKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVAA TGDGPDIIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNGKLIAYPIAVEA LSLIYNKDLLPNPPKTWEEIPALDKELKAKGKSALMFNLQEPYFTWPLIAADGGYAFKYE NGKYDIKDVGVDNAGAKAGLTFLVDLIKNKHMNADTDYSIAEAAFNKGETAMTINGPWAW SNIDT SKVNYGVTVLPTFKGQPSKPFVGVLSAGINAAS PNKELAKE ELENYLLTDEGLEA VNKDKPLGAVALKSYEEELVKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINAAS GRQTVNEALKDAQTGPRTGSLVPRGSASENLDFQGMSIYQEFMSRETNFNGTKRKRSDVA EKVAQRWKSVRYSAEMENMAPVNSNNDSDDCVIVSESKIIDLTNQEQDLSERIGTNDTAK GAVFKLMKSDFYEREDFMGEVEDMITLKDIFGTETLKRSILFSFQYELDFLLRQFHQNVE NITIVGQKGTIMPIEARAMDATLAVILKKVKLIEITMPPFASHHTKLIINFYDNGECKIF LPSNNFTSMETNLPQQVCWCSPLLKIGKEGLPVPFKRSLIEYLNSYHLKDIDELITKSVE EVNFAPLSELEFVYSTPSKFQSSGLLSFYNKLEKLSAGTSASDTAKHYLCQTSSIGTSLS RARDENLWTHLMIPLFTGIMSPPAKDTAGRKKAEILPTNSLINEYSQRKIKPYIIFPTEQ EFVTSPLKWSSSGWFHFQYLQKKSYYEMLRNKFKVFYKQDPAMVTRRRGTTPAHSKFYMH CATNSTGPCDASQVFKELEWCLYTSANLSQTAWGTVSRKPRNYEAGVLYHSRRLANTRKV TCRTFTRDRRGCAGNPTHVAVPFTLPVIPYDLAEDECFCLARHEND (SEQ ID NO: 4) The 3’-phosphate of the oligonucleotide probe was attached by way of thiol-maleimide linkage to horse radish peroxidase (HRP). The 5’-end was immobilized by way of strain-promoted azide-alkyne cycloaddition (SPAAC) on a poly(methylmethacrylate) (PMMA) bead, so that hydrolysis of the 3’-phosphate would release HRP from the solid support (see Figure 4A). A cellulose wick was then used to separate bead-immobilized (i.e. unprocessed) and free HRP, and enable mixing of the free HRP with a 3,3’, 5,5’-tetramethylbenzidine (TMB) substrate solution to generate a blue reaction product. Thus, a mRPA reaction containing target amplicon should produce a blue colour on a wick, whilst a no template control (NTC) should be colourless. Materials and methods Bead-immobilized HRB-labelled probe oligonucleotides Lyophilized DBCO-labelled oligo was purchased from ATDBio Ltd (UK) with the following sequence and modifications (see Figure 4 A and B): 5’_[DBC0(TEG)]- rGECTGC A AGTCCTA AGAEGrC A ATGGA A A AGA A ACACGCGGATGA A A-FTFG-A-J / A. A_J A—xA. A A~x / A. xAxA. A_J x A. A-J A—> AxA A. A»_J xAxAx Ax A A_J xAx Ax A x AA— / A*_J A~x A-J A-J x A A A_J x Ax AI A A * x 4 A»_J C6SS_3’ (SEQ ID NO: 121); where: DBCO(TEG) represents dibenzocyclooctyne attached through a tetra(ethylene glycol) linker; HEG represents hexa(ethylene glycol) linker; C6SS represents a dithiol modifier; denotes a phosphate linkage between modifiers. Click Buffer = 12 mM sodium phosphate pH 8.5; 137 mM NaCl; 510 mM MgCL, 0.1 % w / v SDS. 5 mm azide-functionalized PMMA beads (210 mL of a 1 % w / v stock from PolyAn GmbH (Germany)), Click Buffer (350 mL), and DBCO-labelled oligo (50 mL of a 100 mM solution in Click Buffer) were reacted overnight in the dark at room temperature. The reaction mixture was then centrifuged for 1 min at 4,000 g, supernatant was removed, and the labelled beads were washed centrifugally (1 min at 4,000 g) x3 with 500 mL of 0.2 M sodium phosphate pH 8.5, 0.1 % v / v NP40. Beads were resuspended in 200 mL of 0.2 M sodium phosphate pH 8.5, 0.1 % v / v NP40, to yield approx. 1 % w / v of oligo-labelled beads. Maleimide Conjugation Buffer = 0.1 M sodium phosphate pH 7.2, 5 mM EDTA, 0.1%v / vNP40. Storage Buffer = 25 mM Tris.OAc pH 8.3, 7.5 mM KOAc, 0.0125 % v / v NP40. To attach maleimide-HRP to thiolated oligos on PMMA beads, a suspension (500 mL) of 80 mM DTT and 0.2 % w / v of oligo-labelled beads (with 3’-dithiol) was rotated for 30 min at room temperature. The reaction mixture was then centrifuged for 1 min at 4,000 g, supernatant was removed, and the beads were washed centrifugally (1 min at 4,000 g) x4 with Maleimide Conjugation Buffer (400 mL), then resuspended in Maleimide Conjugation Buffer (160 mL) containing 2 mg of EZ-link maleimide HRP, and rotated for 3.5 hours at room temperature (NB. Thermo EZ-Link Maleimide HRP # 3148; this is a 5 mg pack size, but the total solid content is 25 mg - weights in the protocol above refer to this total solid). The reaction mixture was then centrifuged for 1 min at 4,000 g, supernatant was removed, and the beads were washed centrifugally (1 min at 4,000 g) x5 with Storage Buffer, then resuspended in 100 mL of Storage Buffer to give approx. 1 % w / v beads labelled with HRP-oligo. To check HRP labelling - mix 1 mL of bead suspension (or supernatant to check leaching or wash) with 100 mL TMB substrate solution (Abeam # 171522, warmed to room temperature), then add 900 mL IM HC1 aq. and measure A450. If HRP is present, then a blue colour develops - addition of HC1 stops the reaction and gives a yellow solution. The target locus to which the probe binds is shown in Figure 4B (SEQ ID NO: 122). HRP release by yeast TDP-1 5 mm PMMA beads functionalized with HRP-labelled probe oligonucleotides were freshly washed centrifugally (4,000 g for 1 min) x4 with 25 mM Tris acetate pH 8.3, 7.5 mM KOAc, 0.0025 % v / v Triton X-100 (400 uL), then resuspended to approx. 1 % w / v in 25 mM Tris acetate pH 8.3, 7.5 mM KOAc, 0.0025 % v / v Triton X-100. mRPA reactions were performed for 20 min at 42 °C with standard mRPA protein and buffer concentrations, and 0.02 % w / v of freshly washed oligo-HRP labelled PMMA beads, with 104 copies of hly template or no template, with or without 22.3 pmol of yTDPl enzyme. Reactions contained 0.8 mM of each of the following primers: Forward primer sequence: 5 ’ -AAATTTA ATTTC ATCC ATGGC ACC ACC AGC ATCTC-3 ’ (SEQIDNO: 123) Reverse primer sequence: 5 ’ -CTGC ATCTCCGTGGT ATACTAATACATTGTTTTTA-3 ’ (SEQ ID NO: 124) Reactions contained 33 .6 mM magnesium acetate. At the end of the RPA reactions, backed wicks (Ahlstrom 222) were inserted into reaction tubes for 3 min, then inverted and inserted into TMB substrate solution (100 mL) for 10 min; a blue colour showed HRP release. Results The HRP blue colour was yeast TDP1 dependent, and was more intense for positive (i.e. 104 copy) reactions than forNTCs (see Figure 4C). Conclusions The results of this experiment were consistent with target-specific probe processing and release of HRP by yTDPl. Example 3. Development and Characterisation of an Oligo-Hemin Probe -Enzyme / Co-factor System - Colorimetric Detection. Purpose and summary of experiment Horse radish peroxidase (HRP) is an enzyme commonly used for diagnostic application for its ability to generate a colorimetric signal after oxidization of commercially available substrates. The enzyme contains a hemin cofactor centre which is essential for catalysis. By acid treatment of the enzyme, it is possible to remove the cofactor (generating this way an apo-enzyme). The apo-enzyme alone is unable to perform any catalysis. The inventors produced an oligo-hemin conjugate which can be tested for its ability to reconstitute the apo-enzyme. The purpose of the experiments was to show initially that (i) the apo-horse radish peroxidase does not generate any activity, (ii) whether a nuclease is necessary for reconstitution, and (iii) that Gp32 stops reconstitution by binding to and “cloaking” the probe. Nuclease activity would release the hemin cofactor from the probe. However, Gp32 binds to single-strand DNA and by doing so it is able to sterically hinder certain process such as nuclease-processing. The inventors tested HRP activity by following the oxidative coupling of p-hydroxybenzoic acid with 4-aminoantipyrine in the presence of hydrogen peroxide which results in the formation of a quinoneimine dye (red colour). To avoid addition of hydrogen peroxide this compound was produced in situ by adding glucose oxidase and glucose. Materials and methods Oligonucleotide hemin conjugate synthesis A 3’-NH2 probe oligonucleotide was produced with sequence specific to the COVID E gene and FluA NS region: COVID E gene: 5’- GGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTG-3’(NH2) (SEQ ID NO: 125) FluANS region: 5’- TACAGAGATTCGCTTGGAGAAACTGTGATGAGAATGGGAGACCTTCACTACCT -3’(NH2) (SEQ ID NO: 126) Synthesis was performed on a 1 mmol scale using standard automated phosphoramidite chemistry on a K&A H2 oligo synthesizer; the amino modification was introduced using 3'-PT-Amino-Modifier C3 CPG (Glen Research (USA)). Cleavage and deprotection was performed at 65 °C for 15 min using AMA (i.e. 1:1 v / v cone. NH3 aq. / conc. MeNH? aq.); purification was by RP-cartridge (Glen Research (USA)) and then IP-RP-HPLC on a Waters OST C18 column using a gradient of acetonitrile in 50 mM TEAA aq. pH 7. Desalting was performed using a NAP-10 SE column (Cytiva (USA)). Oligos were characterized by LCMS on a Waters BioAccord instrument in negative ionization mode; LC separation was by HILIC using a Waters BEH amide column in 10 mM ammonium acetate and a gradient of water in acetonitrile. A mixture of hemin (0.1 M) and O-(Benzotriazol-l-y])-A'..V,V,V-tetramethyluronium hexafluorophosphate (HBTU, 0.1 M) in DMF were reacted briefly (5 min), then 40 mL was added to 125 nmol of amino-modified oligo in 60 mL of 0.5 M pH 9 NaHCOa aq. and reacted at room temperature overnight (16 h). The crude target was desalted into Milli-Q H2O (1.5 mL) by NAP-10 SE column, then lyophilized overnight and redissolved in Milli-Q water (1 mL). An insoluble brown precipitate was removed by centrifugal filtration (Corning (USA) Costar 0.22 mm CA filter) then concentrated using an Amicon ultra 0.5 10 kDa MWCO filter, washing centrifugally with additional Milli-Q water to remove free hemin. The remaining volume (approx. 145 mL) was purified by IP-RP-HPLC on a Waters OST C18 column using a gradient of acetonitrile in 50 mM TEAA aq. pH 7. Target fractions were lyophilized, then redissolved in Milli-Q water and desalted by NAP-10 SE. Target hemin-labelled oligo was characterized by LCMS as above. Preparation of apo-HRP and biochemical assays Horse radish peroxidase, glucose oxidase and catalase were purchased from Sigma. Gp32 and nuclease (NExo from Neisseria meningitidis, an ExoIII family AP endonuclease) were produced recombinantly using E. coli. Apo-HRP was prepared using the following protocol. Horse radish peroxidase (10 mg / mL, in H2O, 2 mL) was kept cold by keeping it on ice. Concentrated acid (HC1) was then added to the protein mix to reach at least pH 2. An equal volume (2 mL) of 2-butanone was used to separate the hemin from the protein: upon mixing, the hemin (brown) would go to the organic phase while the lower aqueous layer contained the protein. The organic phase was then discarded. The procedure was repeated more than 10 times until the lower aqueous layer was colourless. Finally, the aqueous layer was dialysed overnight against a buffer containing 20 mM Tris, 10 % glycerol, pH 8. The enzyme was then stored at -20°C. Unless specified otherwise all the colorimetric assays have been carried with the following protocol. A stock solution 5x (solution B) of buffer containing 50 mM Tris, Glucose oxidase (Sigma, 1 mg / mL), 10 mM p-hydroxybenzoic acid (Fisher scientific), 0.5 mM 4-aminoantipyrine (Sigma) was prepared. Colourimetric reactions were assembled in a buffer (solution C) containing 50 mM Tris (pH 8), 28 mM MgCL, solution B lx, 1% DMSO, 20 mM Glucose. Depending on the reaction condition the oligo-hemin and / or Gp32 and NExo were supplied to the mix typically to a final concentration of 25 nM, 0.7 mg / mL and 0.07 mg / mL respectively. The reaction was initiated by addition of qpo-HRP (to 25 ug / mL) and then incubated at 37 °C for 5-15 minutes as per the following reaction scheme for the in situ generation of hydrogen peroxide and oxidative coupling of p-hydroxybenzoic acid with 4-aminoantipyrine catalysed by horse radish peroxidase (HRP): cts Gluconic acid k X A H>02 + Gluconofactone nKr Results The inventors sought to determine whether the oligo-hemin probe can reconstitute apo-HRP and if Gp32 is able to stop the reconstitution via binding the probe. Figure 5A shows the initial results of the reconstitution of apo-HRP using the synthesized heminoligo probe (Reaction conditions - Solution C: 50 mM Tris, 28 mM MgCh, 20 mM glucose, 50 ug / mL glucose oxidase, 2 mM 4-hydroxybenzoic acid and 100 uM 4-aminoantipyrine - see Material and Methods section). After setting up the reactions the plate was incubated at 37°C for 10 minutes. Well #1 (numbering from left to right) contains only the buffer: the solution remains colourless hence as expected no catalysis occurs without horse radish peroxidase addition. Well #2 is the positive control: addition of functional horse radish peroxidase (HRP, to 25 ug / mL) produces a colour change. In wells 3-5 the hemin-oligo probe was added to Solution C. Figure 5A shows that no colour change occurs by adding the oligo probe to a final concentration of 25 nM. Well 6 shows the addition of apo-horse radish peroxidase to Solution C: almost no background activity is observed in the apo-enzyme (the solution remains transparent). Wells 7-9 show that by combining the apo-HRP and oligo-hemin probe the result is different and an intense red colour was observed. The same red colour was observed in the presence of a nuclease (NExo). These results prove that the single components of the reaction are not able to generate a colour change, while the oligo-hemin is able to reconstitute the apo-enzyme irrespective of processing by a nuclease. The experiment was repeated (Figure 5B) using the same experimental conditions as described above. Tube 1 and tube 2 (numbering from left to right) are the controls and, as expected, in the presence of oligo-hemin alone no colour change is observed (Tube #2) while the apo-HRP alone shows only a faint colour change (Tube #1). Combination of apo-HRP and hemin-oligo probe generates a colour change regardless of the presence of nuclease (NExo) (Tube #3 without NExo and Tube #4 with NExo). A very important result is shown in Tubes 5 and 6 (Figure 5B): they show the effect of Gp32 in the presence of apo-HRP and oligo-hemin with and without NExo. In both cases no colour change is observed, proving that Gp32 stops the enzyme reconstitution. A further repeat (same reaction conditions) is shown in Figure 5C and the reaction was monitored after 5 and 15 minutes. The controls (wells#l-3) remain transparent while a colour change is observed when apo-HRP and oligo-hemin probe are in the same mixture regardless of nuclease activity, even after 5 minutes (wells #4-6 without NExo and wells #10-12 with NExo). Again, the presence of Gp32 inhibits the reconstitution reaction (wells #7-9). The inventors also investigated whether the Gp32 effect is due to binding to the probe, i.e. steric hinderance, rather than any effect on the colorimetric reaction. This was tested by adding Gp32 to a solution containing functional Ao / o-horse radish peroxidase. Given that no oligonucleotide probe is involved in the reaction of hemin-containing horse radish peroxidase we expect to see a colour change in the presence of Gp32. Addition of holo-HRP (containing hemin) to the reaction buffer (solution C; see Methods and Results section for concentrations) caused a colour change with and without Gp32 (Figure 6). This observation confirms that the Gp32 effect observed in Figure 5 is to stop the reconstitution of apo-horse radish peroxidase via protection of the oligo-hemin probe. Together with the results described above, this demonstrates that Gp32 prevents the reconstitution of apo-HRP by an oligo-hemin probe. Conclusions The inventors have successfully demonstrated that an oligo-hemin probe is able to reconstitute an apo-horse radish peroxidase and that the reconstitution is impaired by the presence of Gp32. The inhibition mediated by Gp32 has been shown to arise as a consequence of Gp32 binding to single-stranded DNA portion of the probe, thereby sterically hindering the reconstitution of hemin and apo-HRP. Example 4. Detection of RPA Products Using an Oligo-Hemin Probe - Enzyme / Co-factor System with Colorimetric Detection. Purpose and summary of experiment After the successful characterisation of an oligo-hemin probe described in Example 3, the inventors then investigated whether the reconstitution of the qpo-HRP could be used to monitor recombinase polymerase amplification (RPA). For the purposes of assessing whether RPA amplification could be monitored using the oligo-hemin / apo-HRP detection system a two-pot reaction system was investigated. In this experiment, the hemin-oligo probe was supplemented to the RPA mix. After 20 minutes, the volume was transferred to a new tube containing the components required for colour change. Materials and methods RPA amplification was set up using in-house recombinant enzymes (18.23 ng / uL Epi polymerase, 110 ng / uL Creatine Kinase, 58.36 ng / uL UvsX, 14.99 ng / uL UvsY and 13.12 ng / uL ExoIII) and a buffer containing (25 mM Tris Acetate pH 8.3, 1% DMSO). Primers (forward and reverse) were used to 0.8 uM and Gp32HRP to 0.7 mg / mL. Other components in the standard RPA mix are Potassium Acetate (7.5 mM), ATP (2.5 mM), phosphocreatine (20 mM), dNTPs (1 mM). The hemin-Flu-probe was added to 180 nM. Reactions were initiated by addition of a solution of MgOAc to 28 mM containing either water or FluA DNA. Reactions were then incubated at 42°C for 20 minutes. A separate tube was prepared with 180 uL of a buffer containing (50 mM Tris acetate (pH 8.3), 28 mM MgCh, solution B lx, 1% DMSO, 20 mM Glucose); solution B is a 5x stock solution containing 50 mM Tris acetate (pH 8.3), Glucose oxidase (Sigma, 1 mg / mL), 10 mM p-hydroxybenzoic acid (Fisher scientific), 0.5 mM 4-aminoantipyrine (Sigma) and apo-HRP to 25 ug / mL. A volume of 25 uL of RPA mix was then transferred to the 180 uL of colorimetric mix and further incubated for 10 minutes. Results The inventors assessed the qpo-HRP RPA reaction in a two-pot system (Figure 7; three negative (i.e. no template) controls (ntc) and three positive reaction - 3xl04 c / uL). The no template controls remained pale pink in colour while the positive samples showed a strong red colour (Figure 7). Conclusions Detection of successful amplification was observed via reconstitution of apo-HRP via the oligo-hemin probe. Example 5. Development and Characterisation of Linear Oligo-Alpha-Peptide Probes - Peptide Activator System - Colorimetric Detection. Purpose and summary of experiment The beta-galactosidase enzyme fragment complementation assay may be coupled to mRPA for read-out, through attachment of the alpha peptide fragment to an oligonucleotide probe in such a way that the peptide is constrained and blocked from complementing the omega fragment until it is released from the oligo or otherwise liberated relative to the oligo by e.g. a nuclease, such as Exo III, in the presence of target amplicon. Thus, beta-galactosidase is activated by mRPA in a target specific manner. Whilst a colorimetric detection system was demonstrated in the present example, the choice of beta-galactosidase enzyme substrate permits the same system to be used for multiple detection methods (e.g. colourimetric, fluorescence, chemiluminescence, bioluminescence and electrochemical detection). Multiple sites and modes of attachment are possible for alpha peptide-oligo conjugates. SPAAC was used to attach the N- and C- termini of the alpha-peptide to the oligo. The inventors synthesised and characterised the following linear probe constructions, namely: (i) a conjugation between the N-terminus of the alpha-peptide to the 3’ terminus of the oligonucleotide (Figure 8A); (ii) a conjugation between the C-terminus of the alpha-peptide and the 3’terminus of the oligonucleotide (Figure 8B); and (iii) a sandwich construct comprising an alpha-peptide conjugated to two oligonucleotides (at their 3’ ends), with one oligo conjugated to the N-terminus of the alpha-peptide and the other oligo conjugated to the C-terminus of the alpha-peptide (Figure 8C). Materials and methods 3’-NH2 probe oligonucleotides were produced with sequences specific to a given target, e.g. forRSVB: 5’ - TCTTGATCTGTCGCTTTCAGAGAACTTCAACTTTTCAT(NH2)-3’(NH2) (SEQ ID NO: 127) Synthesis was performed on a 1 pmol scale using standard automated phosphoramidite chemistry on a K&A H2 oligo synthesizer; the dT-amino modification was introduced using a phosphoramidite from Glen Research (CAS 198080-39-6); the 3’-amino modification was introduced using 3'-PT-Amino-Modifier C3 CPG (Glen Research (USA)). Cleavage and deprotection was performed at 65 °C for 15 min using AMA (i.e. 1:1 v / v cone. NEE aq. / conc. MeNH2 aq.); purification was by RP-cartridge (Glen Research (USA)) and then IP-RP-HPLC on a Waters OST C18 column using a gradient of acetonitrile in 50 mM TEAA aq. pH 7. Desalting was performed using a NAP-10 SE column (Cytiva (USA)). Oligos were characterized by LCMS on a Waters BioAccord instrument in negative ionization mode; LC separation was by HILIC using a Waters BEH amide column in 10 mM ammonium acetate and a gradient of water in acetonitrile. Amino-modified oligo was subsequently labelled with DBCO-NHS ester (Merck, CAS 1353016-71-3); 80 pL of DBCO-NHS ester at 25 mM in DMSO was added to 124 nmol of bis-amino-modified oligo in 120 pL of 0.5 M pH 8.8 NaHCOs aq. and reacted at 40 °C for Ih. An additional 25 pL of DBCO-NHS ester at 25 mM in DMSO was added and reaction continued for a further 1 h at 40 °C. The crude target was desalted into Mi 11 i-Q H2O (1.5 mL) by NAP-10 SE column, then concentrated to dryness on a Speedvac overnight. The sample was then redissolved in 0.1 mL of 0.1 M TEAA aq. pH7, and purified by IP-RP-HPLC on a Waters OST C18 column using a gradient of acetonitrile in 50 mM TEAA aq. pH 7. Target fractions were concentrated to dryness on a Speedvac overnight, then redissolved in Milli-Q water, desalted by NAP-10 SE and lyophilized overnight before characterization by LCMS as above. Bis-DBCO-labelled oligonucleotide was reacted with bis-azidoacetyl-functionalized peptide from CPC (China), see sequence below: Azidoacetyl-MTMITDSLAVVLQRRDWENPGVTQLNRLAAHPPFASWRNSEK (Azidoacetyl)-NH2 (SEQ ID NO: 128) Bis-DBCO-oligo (70 nmol) and bis-azide-peptide (70 nmol) were mixed in 350 pL of 0.1 M TEAA pH 7 aq. containing 4 % v / v DMSO, and 70 pl of formamide was then added to dissolve the appearing precipitate. The reaction mixture was left at room temperature for 6 hours, followed by addition of 14 nmol of peptide in DMSO (2.8 pL) and the reaction was continued over the weekend (64 h) at approx. 4 °C. 47 pl of 3M K acetate buffer (pH5.5) was added, and the conjugate was precipitated with 1.18 ml of ethanol (abs) at -20°C for 1 h. Conjugate was pelleted at 17,000 g for 20 minutes, the supernatant discarded and pellet dissolved in 380 pl of water first, followed by addition of 20 pL 3M K acetate buffer (pH 5.5). Precipitation with 1 mL of ethanol (abs) at -20°C for 1 h and pelleting was repeated as above, then the pellet was dried in by Speedvac briefly (5 min) and redissolved in 100 pl of 0.1 M TEAA aq. pH7. The conjugate was then redissolved in 0.1 mL of 0.1 M TEAA aq. pH7, and purified by IP-RP-HPLC on a Waters OST C18 column using a gradient of acetonitrile in 50 mM TEAA aq. pH 7. Target fractions were concentrated to dryness on a Speedvac overnight, then redissolved in 0.1 mL of 20 mM Tris.HCl aq. pH 8.0 and purified by IEX-HPLC on a Thermo DNAPac PA200 column, using a gradient of NaCl in 20 mM Tris.HCl aq. pH 8.0. Fractions containing conjugate were desalted using an Amicon ultra 0.5 10 kDa MWCO filtration unit by replacing the elution buffer with Milli-Q water three times. Final desalted conjugate was recovered from the filter in approximately 60 pL volume and characterized by LCMS as above. The sequence of the oligonucleotide shown in Figure 8A is set forth in SEQ ID NO: 129. The sequence of the alpha peptide shown in Figure 8A is set forth in SEQ ID NO: 130. The sequence of the oligonucleotide shown in Figure 8B is set forth in SEQ ID NO: 131. The sequence of the alpha peptide shown in Figure 8B is set forth in SEQ ID NO: 132. The sequence of the oligonucleotides shown in Figure 8C is set forth in SEQ ID NO: 133. The sequence of the alpha peptide shown in Figure 8C is set forth in SEQ ID NO: 134. The sequence of the alpha peptide shown in Figure 8E is set forth in SEQ ID NO: 135. Alpha complementation experiments Alpha complementation experiments were carried out with the following conditions: 25 mM Tris Acetate, 28 mM Mg acetate, 7.5 mM K acetate (pH 8.3). Unless specified otherwise the buffer was supplemented with 20 nM oligonucleotide-alpha peptide conjugate, colorimetric substrate CPRG (chlorophenol-red P-d-galactopyranoside) to 1 mM, ExoIII to 0.07 mg / mL and gp32 to 0.7 mg / mL. Reactions were initiated by addition of omega fragment (purchased from Molecular Depot, final concentration: 18 uM) unless specified otherwise. Electrochemical alpha-complementation was carried out with the following conditions: 25 mM Tris acetate (pH 8.3), 28 mM MgCL, 12.5 mM ANPG unless specified otherwise. The proteins Exo III, Gp32 and Omega were injected to reach the final concentrations 0.07 mg / mL, 0.7 mg / mL and 1.8 uM respectively. An off-the shelf screen printed carbon electrode (WE: carbon - 0.5 cm2; CE: carbon; RE: Ag / AgCl) was purchased from Flexmedical (UK). Chronoamperometry conditions: + 0.3 V vs. Ag / AgCl, 42°C. RPA colorimetric experiment was carried out with the following conditions: Table 1 - List of components involved in the colorimetric mRPA experiments LacZ free Protein mix: • Epidermidis-Polymerase (Pol, 37 ng / uL) • Creatine kinase (CK, 110 ng / uL) • UvsX (343 ng / uL) • UvsY (88 ng / uL) • Exonuclease III (ExoIII, 57 ng / uL) • Omega fragment (1.8 uM) Other components: • 25 mM Tris acetate (unless specified otherwise) • Triton X-100 (0.0125 %) • dNTPs(lmM) • ATP (2.5 mM unless specified otherwise) • Phosphocreatine (20 mM) • Potassium acetate (7.5 mM) • Forward primer (0.8 uM) • Reverse primer (0.8 uM) • alpha-peptide probe • Gp32 or Gp32HRPl (0.65 mg / mL) • Magnesium acetate (28 mM) • Template viral DNA • 35 K 5.5% PEG (unless specified otherwise) • CPRG (1 mM) The reactions were assembled by first combining all the reagents except for magnesium and template. Their addition initiated the reaction which was left on a heating block at 42°C. Results 1. Results for linear probe having the structure: 5’-oligo-3’-N-alpha peptide-C-term fN-terminus conjugate') The inventors sought to determine whether the N-terminus conjugate probe (as depicted in Figure 8A) complemented the omega fragment and whether nuclease (ExoIII) processing is needed for the process to occur. Moreover, the inventors investigated Gp32 protection of the oligonucleotide probe from ExoIII processing. The purpose of the testing was to determine: (i) whether the oligo-alpha-peptide probe is able to complement the omega fragment by itself; (ii) whether ExoIII processing of the probe causes a speed-up of alpha-compl ementati on; (iii) whether Gp32 protects the probe from alpha-complementation; and (iv) whether Gp32 protects the probe from ExoIII processing and hence from alpha-complementation. Experimental conditions: The experiment was carried out in a buffer (30 uL) containing 25 mM Tris Acetate, 20 mM Mg acetate, 7.5 mM K acetate (pH 8.3). The buffer was supplemented with colorimetric substrate (CPRG) to 1 mM. Processing of the substrate causes a release of chlorophenol-red and the solution turns from yellow to red (lambda max: 575 nm). Initial results were carried out with the N-terminus alpha peptide oligo probe and results are shown in Figure 9. The PCR tubes contain different combinations of the components involved: Tube #1-3: From tube #1 to 3 the buffer was supplemented with only buffer, omega fragment and + alpha-probe. These control experiments show that the omega and probe by themselves do not cause any colour change (omega injected to 1.8 uM and probe to 20 nM). Tube#4: buffer was supplemented with both omega and probe. Tube#5: buffer was supplemented with omega, probe and ExoIII. We observed a faint colour change after 15 minutes in the tube containing omega and alpha-peptide probe but there was a strong rate increase in alpha-complementation in the presence of Exo III. These data suggest that released alpha-peptide (release catalysed by Exo III) complements better than the unprocessed oligo conjugate. Tube #6: buffer was supplemented with omega, alpha peptide, probe and Gp32. Tube #7: buffer was supplemented with omega, alpha peptide, probe, Gp32 and Exo. Ill We observed alpha-complementation in both tubes #6 and #7. A visible colour difference between tube 5 and tubes 6-7 was observed, suggesting that Gp32 protects the probe from alpha-complementation (Figure 9). Conclusion Nuclease (Exo III) processing of the N-terminus conjugate probe leads to alpha complementation following release of Gp32. A colour change was observed in all the tested conditions. 2. Results for linear probes having the structures: (a) 5’-oligo-3’-C-alphapeptide-N-term (‘C-terminus conjugate’); and (h) 5’-oligo-3’-N-alpha-peptide-C-term-3’-oligo-5’ (‘sandwichprobe’) The inventors sought to determine whether the C-terminus conjugate and the sandwich probe (as depicted in Figures 8B and 8C respectively) complemented the omega fragment and whether nuclease (Exo III) processing is needed for the process to occur. Moreover, the inventors investigated Gp32 protection of the oligonucleotide probes from nuclease (Exo III) processing. The objective was to determine the ability of the two new probe arrangements to drive alpha complementation by themselves, the enhancement of alpha-complementation kinetics after nuclease processing and, very importantly, the ability of Gp32 to protect the probe from processing and from complementation. Results with the C-terminus conjugate are shown in F...

Claims

1. A method of detecting a target nucleic acid sequence of interest in a test solution, the method comprising:1) providing a test solution comprising:A) a RPA single-stranded DNA-binding protein (RPA-SSB) molecule;B) a cleavage molecule;C) a detection probe comprising a signal-promoting molecule; andD) a sample suspected of comprising a target nucleic acid sequence of interest; and2) detecting a detectible signal produced by the signal-promoting molecule of the probe, upon:A) hybridisation of the one or two oligonucleotides of the probe with the target nucleic acid sequence of interest; andB) cleavage at the cleavage site of the probe by the cleavage molecule, wherein cleavage occurs by the action of phosphatase or exonuclease activity, and not by apurinic / apyrimidinic (AP) endonuclease activity;wherein the probe comprises a signal-promoting molecule which is:I. a polypeptide, preferably which:A) has enzymatic activity;B) is a component of an enzyme complex, is a domain of an enzyme, is a fragment of an enzyme or is an enzyme cofactor; orC) is an activator of an enzyme or an enzyme complex;and wherein the probe is a probe according to any one of claims 25 to 44; orII. a small molecule, preferably which:A) promotes the formation of a molecular complex, such as a protein:protein complex;B) promotes the activation of an enzyme or an enzyme complex; or09 12 24C) is a cofactor of an enzyme or an enzyme complex;and wherein the probe is a probe according to any one of claims 25 to 37 and 45 to 47;2. A method according to claim 1, wherein the test solution is a RPA reaction mixture comprising RPA reaction components, wherein in addition to the RPA-SSB, the RPA reaction components comprise:1) a recombinase agent;2) a recombinase loading protein;3) a polymerase; and4) forward and reverse nucleic acid primers for amplification.

3. A method according to claim 2, wherein after the providing step (A), the method further comprises performing a RPA reaction comprising one or more cycles of amplification, and detecting the detectible signal during the one or more cycles of amplification in real time, or at the end of the one or more cycles of amplification.

4. A method according to any one of claims 1 to 3, wherein the RPA-SSB is selected from the group consisting of Gp32, E. coli SSB protein, phage T4 Gp32 protein, phage Rb69 Gp32, phage vB EcoM NBGl Gp32, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably the RPA-SSB is Gp32 or phage vBEco\1_\ Gp32, optionally wherein the RPA-SSB is tagged with one or more functional intrinsically disordered regions (IDRs), preferably as a genetically engineered fusion protein comprising the RPA-SSB and an amino acid sequence comprising or consisting of the one or more functional IDRs.09 12 245. A method according to any one of claims 2 to 4, wherein the recombinase agent is selected from the group consisting of UvsX, T4 UvsX, T6 UvsX, RBI8 UvsX, E.coli phage wV7 UvsX, Shigella phage CB8 UvsX, Shigella phage Shfl2 UvsX, E.coli phage ARI UvsX, phage xBEcoM^G UvsX, Shigella phage SHFML-11 UvsX, Escherichia phage vBEcoXID UvsX, E. coli RecA, E. coli RadA, E. coli RadB, E. coli Rad 51 or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the recombinase agent is UvsX, more preferably Escherichia phage vBEcoMDalCa UvsX.

6. A method according to any one of claims 2 to 5, wherein the recombinase loading protein is selected from the group consisting of UvsY, E. coli RecO, E. coli RecR or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the recombinase loading protein is UvsY, more preferably Escherichia phage STO UvsY.

7. A method according to any one of claims 2 to 6, wherein the polymerase is:1) a eukaryotic polymerase selected from the group consisting of pol-a, pol-P, pol-5, pol-s or any functional analog, homolog or derivative thereof, and any combination thereof;2) a prokaryotic polymerase selected from the group consisting of Bacillus stearothermophilus polymerase I large fragment, Bacillus subtilis Pol I large fragment (Bsu polymerase), Listeria monocytogenes DNA polymerase I, S. aureus DNA polymerase I (Sau polymerase), E. coli DNA polymerase I Klenow fragment, E. coli DNA polymerase I, E. coli DNA polymerase II, E. coli DNA polymerase III, E. coli DNA polymerase IV, E. coli DNA polymerase V, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably wherein the polymerase is S. aureus DNA polymerase I (Sau polymerase) or Bacillus subtilis Pol I large fragment (Bsu polymerase);09 12 243) a bacteriophage polymerase selected from the group consisting of bacteriophage T4 gp43 DNA polymerase, T7 DNA polymerase and Phi-29 DNA polymerase, or any functional analog, homolog or derivative thereof, and any combination thereof.

8. A method according to any one of claims 1 to 7, wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; wherein the cleavage molecule is Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 2; or wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4.

9. A method according to any one of claims 1 to 8, wherein the probe is a probe according to claim 38, and wherein the detectible signal is produced in a reaction which is dependent upon the polypeptide of the probe.

10. A method according to claim 9, wherein the probe is a probe according to claim 39, and wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the polypeptide of the probe.

11. A method according to claim 10, wherein the probe is a probe according to claim 40 or 41, and wherein the detectible signal is produced in a reaction in a solution which is dependent upon the enzymatic activity of HRP of the probe, the method comprising detecting the activity of the HRP enzyme (HRP holoenzyme) in the solution, optionally wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), optionally wherein TDP-1 has the amino acid sequence as set forth in SEQ ID NO: 3 or SEQ ID NO: 4.09 12 2412. A method according to claim 9, wherein the probe is a probe according to claim 42, and wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the enzyme complex comprising the component, the enzymatic activity of the enzyme comprising the domain, the enzymatic activity of the enzyme comprising the fragment, or the enzymatic activity of the enzyme comprising the cofactor.

13. A method according to claim 12, wherein the probe is a probe according to claim 43 or 44, and wherein the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of beta-galactosidase mediated by the betagalactosidase alpha peptide of the probe, optionally wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQIDNO: 1.

14. A method according to claim 12 or 13, wherein the step of detecting the detectible signal comprises:1) contacting the beta-galactosidase alpha peptide of the probe in solution with beta-galactosidase omega fragment (omega peptide) to form beta-galactosidase holoenzyme; and2) detecting the presence of beta-galactosidase holoenzyme in solution.

15. A method according to claim 14, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises: a colorimetric assay, a fluorescence assay, a chemiluminescence assay, a bioluminescence assay or an electrochemical assay.09 12 2416. A method according to claim 15, wherein the step of detecting the presence of beta-galactosidase holoenzyme in solution comprises:1) reacting beta-galactosidase holoenzyme with chlorophenol red-P-D-galactopyranoside (CPRG) in solution, thereby forming a chromophore reaction product chlorophenol red; and2) detecting the presence of chlorophenol red, optionally by measuring the absorbance of the solution at 570 to 595 nm, e.g. 575 nm.

17. A method according to any one of claims 1 to 8, wherein the probe is a probe according to claim 46, and wherein the detectible signal is produced in a reaction which is dependent upon the conversion of an apoenzyme or apoenzyme complex into a holoenzyme or holoenzyme complex mediated by the small molecule cofactor of the probe.

18. A method according to claim 17, wherein the probe is a probe according to claim 47, and wherein the detectible signal is produced in a reaction which is dependent upon the conversion of an apoenzyme or apoenzyme complex into a holoenzyme or holoenzyme complex mediated by the hemin small molecule of the probe.

19. A method according to claim 18, wherein the detectible signal is produced in a method comprising:1) contacting in a solution the hemin of the probe with horseradish peroxidase (HRP) apoenzyme, thereby forming HRP holoenzyme; and2) detecting the activity of HRP holoenzyme in the solution,09 12 24optionally wherein the step of detecting the activity of HRP holoenzyme in the solution comprises reacting HRP holoenzyme in the solution with an oxidase and a substrate for the oxidase, and detecting the presence of a product produced by the reaction.

20. A method according to claim 11 or 19, wherein the step of detecting the activity of HRP holoenzyme in the solution comprises:1) (A) reacting HRP holoenzyme in the solution with:i) glucose, e.g. P-d-glucose, glucose oxidase, p-hydroxybenzoic acid and 4-aminoantipyrine; orii) p-hydroxybenzoic acid, 4-aminoantipyrine and H2O2,thereby forming a chromophore reaction product; and(B) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 504 nm; or2) (A) reacting HRP holoenzyme in the solution with:i) glucose, e.g. P-d-glucose, glucose oxidase and 3,3',5,5'-tetramethybenzidine (TMB); orii) 3,3',5,5'-tetramethybenzidine (TMB) and H2O2,thereby forming a chromophore reaction product; and(B) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 450 nm or 650 nm; or3) (A) reacting HRP holoenzyme in the solution with:i) glucose, e.g. P-d-glucose, glucose oxidase and 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS); orii) 2,2’-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) and H2O2,09 12 24thereby forming a chromophore reaction product; and(B) detecting the presence of the chromophore reaction product, optionally by measuring the absorbance of the solution at 405 nm.

21. A detection probe for detecting a target nucleic acid sequence of interest in a test solution, the test solution comprising a recombinase polymerase amplification (RPA) single-stranded DNA-binding protein (RPA-SSB), a cleavage molecule having phosphatase or exonuclease activity and a target nucleic acid sequence of interest; wherein the probe comprises:1) one or two single-stranded oligonucleotides each comprising a sequence which is complementary to a target nucleic acid sequence of interest; and2) a repressible cleavage-dependent signalling system which:A) comprises a signal-promoting molecule tethered to the oligonucleotide(s) via at least one linker, wherein the at least one linker is attached to the signalpromoting molecule and to a chemical group of the oligonucleotide(s) and thereby defines a cleavage site on the oligonucleotide(s);B) provides a detectible signal which:i) is dependent upon cleavage at the cleavage site by the cleavage molecule by the action of phosphatase or exonuclease activity, andii) following hybridisation of the oligonucleotide(s) with the target sequence, is not dependent upon:a) cleavage of the oligonucleotide(s) at an apurinic / apyrimidinic site (abasic site) of the oligonucleotide(s), e.g. at a 3'-side of an abasic site and / or at a 5'-side of the abasic site, or at a site comprising an abasic furan; orb) cleavage of the oligonucleotide(s) at a mismatch site; andC) is configured so that when the probe is present in the test solution:i) when the oligonucleotide(s) is not hybridised with the target sequence, cleavage at the cleavage site by the cleavage molecule09 12 24is inhibited and production of a detectible signal is thereby repressed; andii) upon hybridisation of the oligonucleotide(s) with the target sequence, the cleavage molecule cleaves at the cleavage site, thereby producing a detectible signal;wherein the signal-promoting molecule of the probe is:I. a polypeptide, and wherein the probe is configured such that when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal is produced in a reaction which is dependent upon the polypeptide; orII. a small molecule, and wherein the probe is configured such that when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal may be produced in a reaction which is dependent upon the small molecule.

22. A detection probe according to claim 21, wherein the linker(s):1) is not attached to an abasic nucleotide or an abasic residue of the oligonucleotide(s), e.g. the sugar molecule of an abasic nucleotide; and / or2) is not attached to the oligonucleotide(s) at a nucleotide or residue position adjacent to a position in the oligonucleotide which is occupied by an abasic nucleotide or an abasic residue.

23. A detection probe according to claim 21 or claim 22, wherein each of the one or two oligonucleotides is about 20 to 70 nucleotide positions in length, preferably between about 30 to 60 nucleotide positions in length.09 12 2424. A detection probe according to any one of claims 21 to 23, further comprising a polymerase extension blocking group attached to the 3’ end of the oligonucleotide(s), optionally wherein the blocking group is a spacer, such as a C3-spacer.

25. A detection probe according to any one of claims 21 to 24, wherein:1) the target nucleic acid sequence of interest is DNA and the detection probe is a detection probe for detecting a target DNA sequence of interest; or2) the target nucleic acid sequence of interest is RNA and the detection probe is a detection probe for detecting a target RNA sequence of interest.

26. A detection probe according to any one of claims 21 to 25, wherein when present in the test solution the recombinase polymerase amplification (RPA) singlestranded DNA-binding protein (RPA-SSB) is selected from the group consisting of Gp32, E. coli SSB protein, phage T4 Gp32 protein, phage Rb69 Gp32, phage vBEcoMNBGl Gp32, or any functional analog, homolog or derivative thereof, and any combination thereof, preferably the RPA-SSB is Gp32 or phage vB_EcoM_NBGl Gp32.

27. A detection probe according to claim 26, wherein the RPA-SSB is tagged with one or more functional intrinsically disordered regions (IDRs), preferably as a genetically engineered fusion protein comprising the RPA-SSB and an amino acid sequence comprising or consisting of the one or more functional IDRs.

28. A detection probe according to any one of claims 21 to 27, wherein the cleavage molecule is Escherichia coli Exonuclease III, preferably having the amino acid sequence set forth in SEQ ID NO: 1; wherein the cleavage molecule is Neisseria gonorrhoeae Exonuclease III, preferably having the amino acid sequence set forth in09 12 24SEQ ID NO: 2; or wherein the cleavage molecule is tyrosyl-DNA phosphodiesterase 1 (TDP-1), preferably having the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4.

29. A detection probe according to any one of claims 21 to 28, wherein in each one of the one or two oligonucleotides the signal-promoting molecule is tethered to the oligonucleotide(s) by a linker which is attached to the signal-promoting molecule and to a chemical group of the terminal nucleotide at the 3’ end of the oligonucleotide(s), preferably to the 3’ terminal phosphate group of the oligonucleotide(s), and wherein:1) the chemical group to which the linker is attached, preferably the 3’ terminal phosphate group, comprises the cleavage site; and2) when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage site thereby producing a detectible signal.

30. A detection probe according to any one of claims 21 to 28, wherein in each one of the one or two oligonucleotides the signal-promoting molecule is tethered to the oligonucleotide(s) by two linkers, wherein: (i) a first linker is attached to a first position on the signal-promoting molecule and to a chemical group at nucleotide position n in the oligonucleotide(s), and (ii) a second linker is attached to a second position on the signal-promoting molecule and to a chemical group at nucleotide position n+x in the oligonucleotide(s) wherein:1) the chemical group on the oligonucleotide(s) to which the first linker is attached comprises the cleavage site, preferably the 3’ terminal phosphate group; and2) when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage09 12 24molecule cleaves at the cleavage site thereby producing a detectible signal; andwherein the terminal nucleotide position at the 3’ end of the oligonucleotide(s) is defined as position n, and subsequent nucleotide positions relative to position n in the direction proximal to the 5’ end of the oligonucleotide(s) are defined as n+x, wherein x is an integer of 0 or more.

31. A detection probe according to claim 30, wherein the chemical group of the oligonucleotide(s) to which the first linker is attached is the 3’ terminal phosphate group at position n of the oligonucleotide(s).

32. A detection probe according to claim 31, wherein:1) the second linker is attached to a chemical group at nucleotide position n in the oligonucleotide(s); or2) the second linker is attached to a chemical group at nucleotide position n+1 in the oligonucleotide(s); or3) the second linker is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), wherein x is an integer of 2 or more.

33. A detection probe according to claim 30, wherein the chemical group of the oligonucleotide(s) to which the first linker is attached is the nucleobase of a nucleotide at position n, preferably a thymine nucleobase.

34. A detection probe according to claim 33, wherein:1) the second linker is attached to a chemical group at nucleotide position n+1 in the oligonucleotide(s); or09 12 242) the second linker is attached to a chemical group at nucleotide position n+x in the oligonucleotide(s), wherein x is an integer of 2 or more.

35. A detection probe according to any one of claims 32 to 34, wherein the chemical group of the oligonucleotide(s) to which the second linker is attached is the nucleobase of a nucleotide, preferably a thymine nucleobase.

36. A detection probe according to claim 30, wherein the second linker is attached to a chemical group which is attached to the terminal nucleotide position at the 5’ end of the oligonucleotide(s), preferably wherein the chemical group is a phosphate group.

37. A detection probe according to any one of claims 21 to 28, wherein the probe comprises two oligonucleotides, and wherein:1) the signal-promoting molecule is tethered to a first oligonucleotide by a first linker which is attached to a first position on the signal-promoting molecule and to a chemical group of the terminal nucleotide at the 3’ end of the first oligonucleotide, preferably to the 3’ terminal phosphate group of the first oligonucleotide; and2) the signal-promoting molecule is tethered to a second oligonucleotide by a second linker which is attached to a second position on the signalpromoting molecule and to a chemical group of the terminal nucleotide at the 3’ end of the second oligonucleotide, preferably to the 3’ terminal phosphate group of the second oligonucleotide;and further wherein:A) the chemical group of the first oligonucleotide to which the first linker is attached, preferably the 3' terminal phosphate group, comprises a first cleavage site, and the chemical group of the second oligonucleotide to09 12 24which the second linker is attached, preferably the 3’ terminal phosphate group, comprises a second cleavage site; andB) when the probe is present in the test solution, upon hybridisation of the oligonucleotide with the target sequence in the presence of a cleavage molecule having phosphatase or exonuclease activity, the cleavage molecule cleaves at the cleavage sites thereby producing a detectible signal.

38. A detection probe according to any one of claims 21 to 37 and wherein the signal-promoting molecule of the probe is according to claim 21(1); wherein when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal is produced in a reaction which is dependent upon the polypeptide.

39. A detection probe according to claim 38, wherein the polypeptide has enzymatic activity, and the detectible signal is produced in a reaction which is dependent upon the enzymatic activity of the polypeptide.

40. A detection probe according to claim 39, wherein the polypeptide is a horseradish peroxidase (HRP) enzyme, preferably wherein the HRP enzyme has the amino acid sequence set forth in SEQ ID NO: 5.

41. A detection probe according to claim 40, wherein the probe has the structure:wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, L is the linker, and HRP is an HRP enzyme, preferably which has the amino acid sequence set forth in SEQ ID NO: 5.09 12 2442. A detection probe according to claim 38, wherein the polypeptide is a component of an enzyme complex, a domain of an enzyme, a fragment of an enzyme or an enzyme cofactor, and the detectible signal is produced in a reaction which is dependent upon the polypeptide.

43. A detection probe according to claim 42, wherein the polypeptide is a betagalactosidase alpha peptide, preferably having an amino acid sequence as set forth in SEQ ID NOS: 6 to 56.

44. A detection probe according to claim 43, wherein the probe has the structure:09 12 24wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, LI is the first linker, and L2 is the second linker.

45. A detection probe according to any one of claims 21 to 37 and wherein the signal-promoting molecule of the probe is according to claim 21(11); wherein when the probe is present in the test solution, upon hybridisation of the oligonucleotide(s) with the target sequence the cleavage molecule cleaves at the cleavage site, whereupon a detectible signal may be produced in a reaction which is dependent upon the small molecule.

46. A detection probe according to claim 45, wherein the small molecule is a cofactor of an enzyme or an enzyme complex, and the detectible signal is produced in a reaction which is dependent upon the activation of the enzyme or enzyme complex.

47. A detection probe according to claim 46, wherein the signal-promoting molecule is hemin, which has the structure:optionally, wherein the probe has the structure:09 12 24rS'-oligonudeotide—o / Lo.wherein * is the terminal phosphate group at the 3’ end of the oligonucleotide, and L is the linker.

48. A composition comprising composition components:1) a RPA single-stranded DNA-binding protein (RPA-SSB) molecule;2) a cleavage molecule; and3) a detection probe according to any one of claims 21 to 47.CM49. A recombinase polymerase amplification (RPA) reaction composition comprising composition components:1) RPA reaction components, including a RPA single-stranded DNA-binding protein (RPA-SSB) molecule,2) a cleavage molecule; and3) a detection probe according to any one of claims 21 to 47.

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