Lessons from Enzyme Kinetics Reveal Specificity Principles for RNA-Guided Nucleases in RNA Interference and CRISPR-Based Genome Editing

Cell Systems

Volumn 4, Issue 1, 2017, Pages 21-29

  Bisaria, Namita ^a   Jarmoskaite, Inga ^a   Herschlag, Daniel ^a,b  

^a STANFORD UNIVERSITY   (United States)

^b Stanford University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGONAUTE PROTEIN; CRISPR ASSOCIATED PROTEIN; GUIDE RNA; NUCLEASE; NUCLEOTIDE; RNA GUIDED NUCLEASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ENDONUCLEASE; ENZYME; RIBONUCLEASE; RNA;

ALLELE; AUTOSOMAL DOMINANT DISORDER; BINDING AFFINITY; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; CONCEPTUAL FRAMEWORK; DISSOCIATION RATE CONSTANT; ENZYME BINDING; ENZYME KINETICS; ENZYME SPECIFICITY; GENE EDITING; GENE MUTATION; GENE TARGETING; GENETIC ENGINEERING; HUMAN; NONHUMAN; PREDICTION; PRIORITY JOURNAL; PROTEIN CLEAVAGE; REVIEW; RNA INTERFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; THERMODYNAMICS; WILD TYPE; CHEMISTRY; CRISPR CAS SYSTEM; GENETICS; KINETICS; PHYSIOLOGY; REPRODUCIBILITY;

CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS; CRISPR-ASSOCIATED PROTEINS; CRISPR-CAS SYSTEMS; ENDONUCLEASES; ENZYMES; GENE EDITING; GENETIC ENGINEERING; HUMANS; KINETICS; REPRODUCIBILITY OF RESULTS; RIBONUCLEASES; RNA; RNA INTERFERENCE; RNA, GUIDE;

EID: 85010672481     PISSN: 24054712     EISSN: 24054720     Source Type: Journal    
DOI: 10.1016/j.cels.2016.12.010     Document Type: Review

References (77)

1. Alber, T.C. (1981). Structural origins of the catalytic power of triose phosphate isomerase. PhD thesis (Massachusetts Institute of Technology).
2. Ameres, S.L., Martinez, J., Schroeder, R., Molecular basis for target RNA recognition and cleavage by human RISC. Cell 130 (2007), 101–112.
3. Bartel, D.P., MicroRNAs: target recognition and regulatory functions. Cell 136 (2009), 215–233.
4. Briggs, G.E., Haldane, J.B., A note on the kinetics of enzyme action. Biochem. J. 19 (1925), 338–339.
5. Carroll, D., Staying on target with CRISPR-Cas. Nat. Biotechnol. 31 (2013), 807–809.
6. Chandradoss, S.D., Schirle, N.T., Szczepaniak, M., MacRae, I.J., Joo, C., A dynamic search process underlies MicroRNA targeting. Cell 162 (2015), 96–107.
7. Dahlgren, C., Zhang, H.-Y., Du, Q., Grahn, M., Norstedt, G., Wahlestedt, C., Liang, Z., Analysis of siRNA specificity on targets with double-nucleotide mismatches. Nucleic Acids Res., 36, 2008, e53.
8. De, N., Young, L., Lau, P.-W., Meisner, N.-C., Morrissey, D.V., MacRae, I.J., Highly complementary target RNAs promote release of guide RNAs from human Argonaute2. Mol. Cell 50 (2013), 344–355.
9. Doench, J.G., Fusi, N., Sullender, M., Hegde, M., Vaimberg, E.W., Donovan, K.F., Smith, I., Tothova, Z., Wilen, C., Orchard, R., et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34 (2016), 184–191.
10. Dua, P., Yoo, J.W., Kim, S., Lee, D.K., Modified siRNA structure with a single nucleotide bulge overcomes conventional siRNA-mediated off-target silencing. Mol. Ther. 19 (2011), 1676–1687.
11. Elkayam, E., Kuhn, C.-D., Tocilj, A., Haase, A.D., Greene, E.M., Hannon, G.J., Joshua-Tor, L., The structure of human argonaute-2 in complex with miR-20a. Cell 150 (2012), 100–110.
12. Fersht, A., Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding. 1999, W.H. Freeman and Company.
13. Fu, Y., Sander, J.D., Reyon, D., Cascio, V.M., Joung, J.K., Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat. Biotechnol. 32 (2014), 279–284.
14. Gasiunas, G., Barrangou, R., Horvath, P., Siksnys, V., Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc. Natl. Acad. Sci. USA 109 (2012), E2579–E2586.
15. Gu, S., Zhang, Y., Jin, L., Huang, Y., Zhang, F., Bassik, M.C., Kampmann, M., Kay, M.A., Weak base pairing in both seed and 3' regions reduces RNAi off-targets and enhances si/shRNA designs. Nucleic Acids Res. 42 (2014), 12169–12176.
16. Guilinger, J.P., Pattanayak, V., Reyon, D., Tsai, S.Q., Sander, J.D., Joung, J.K., Liu, D.R., Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. Nat. Methods 11 (2014), 429–435.
17. Guilinger, J.P., Thompson, D.B., Liu, D.R., Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 32 (2014), 577–582.
18. Haley, B., Zamore, P.D., Kinetic analysis of the RNAi enzyme complex. Nat. Struct. Mol. Biol. 11 (2004), 599–606.
19. Haussecker, D., Kay, M.A., RNA interference. Drugging RNAi. Science 347 (2015), 1069–1070.
20. Hendel, A., Bak, R.O., Clark, J.T., Kennedy, A.B., Ryan, D.E., Roy, S., Steinfeld, I., Lunstad, B.D., Kaiser, R.J., Wilkens, A.B., et al. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat. Biotechnol. 33 (2015), 985–989.
21. Herschlag, D., The role of induced fit and conformational changes of enzymes in specificity and catalysis. Bioorg. Chem. 16 (1988), 62–96.
22. Herschlag, D., Implications of Ribozyme Kinetics for Targeting the Cleavage of Specific RNA Molecules In Vivo: More Isn't Always Better. Proc. Natl. Acad. Sci. U.S.A. 88 (1991), 6921–6925.
23. Hinz, J.M., Laughery, M.F., Wyrick, J.J., Nucleosomes Inhibit Cas9 Endonuclease Activity in Vitro. Biochemistry 54 (2015), 7063–7066.
24. Horlbeck, M.A., Witkowsky, L.B., Guglielmi, B., Replogle, J.M., Gilbert, L.A., Villalta, J.E., Torigoe, S.E., Tjian, R., Weissman, J.S., Nucleosomes impede Cas9 access to DNA in vivo and in vitro. eLife, 5, 2016, e12677.
25. Hu, J.H., Davis, K.M., Liu, D.R., Chemical Biology Approaches to Genome Editing: Understanding, Controlling, and Delivering Programmable Nucleases. Cell Chem. Biol. 23 (2016), 57–73.
26. Isaac, R.S., Jiang, F., Doudna, J.A., Lim, W.A., Narlikar, G.J., Almeida, R., Nucleosome breathing and remodeling constrain CRISPR-Cas9 function. eLife, 5, 2016, e13450.
27. Jackson, A.L., Bartz, S.R., Schelter, J., Kobayashi, S.V., Burchard, J., Mao, M., Li, B., Cavet, G., Linsley, P.S., Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21 (2003), 635–637.
28. Jackson, A.L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J.M., Lim, L., Karpilow, J., Nichols, K., et al. Position-specific chemical modification of siRNAs reduces “off-target” transcript silencing. RNA 12 (2006), 1197–1205.
29. Jiang, F., Zhou, K., Ma, L., Gressel, S., Doudna, J.A., A Cas9-guide RNA complex preorganized for target DNA recognition. Science 348 (2015), 1477–1481.
30. Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., Charpentier, E., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337 (2012), 816–821.
31. Jo, M.H., Shin, S., Jung, S.-R., Kim, E., Song, J.-J., Hohng, S., Human Argonaute 2 has diverse reaction pathways on target RNAs. Mol. Cell 59 (2015), 117–124.
32. Johnson, K.A., Role of induced fit in enzyme specificity: a molecular forward/reverse switch. J. Biol. Chem. 283 (2008), 26297–26301.
33. Khvorova, A., Reynolds, A., Jayasena, S.D., Functional siRNAs and miRNAs exhibit strand bias. Cell 115 (2003), 209–216.
34. Kleinstiver, B.P., Prew, M.S., Tsai, S.Q., Topkar, V.V., Nguyen, N.T., Zheng, Z., Gonzales, A.P.W., Li, Z., Peterson, R.T., Yeh, J.-R.J., et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523 (2015), 481–485.
35. Kleinstiver, B.P., Pattanayak, V., Prew, M.S., Tsai, S.Q., Nguyen, N.T., Zheng, Z., Joung, J.K., High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529 (2016), 490–495.
36. Knight, S.C., Xie, L., Deng, W., Guglielmi, B., Witkowsky, L.B., Bosanac, L., Zhang, E.T., El Beheiry, M., Masson, J.B., Dahan, M., et al. Dynamics of CRISPR-Cas9 genome interrogation in living cells. Science 350 (2015), 823–826.
37. Mali, P., Aach, J., Stranges, P.B., Esvelt, K.M., Moosburner, M., Kosuri, S., Yang, L., Church, G.M., CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol. 31 (2013), 833–838.
38. Martin, F.H., Tinoco, I. Jr., DNA-RNA hybrid duplexes containing oligo(dA:rU) sequences are exceptionally unstable and may facilitate termination of transcription. Nucleic Acids Res. 8 (1980), 2295–2299.
39. Michaelis, L., Menten, M.L., Die Kinetik der Invertinwirkung. Biochem. Z. 49 (1913), 333–369.
40. Michaelis, L., Menten, M.L., Johnson, K.A., Goody, R.S., The original Michaelis constant: translation of the 1913 Michaelis-Menten paper. Biochemistry. Biochemistry 50 (2011), 8264–8269.
41. Miller, V.M., Xia, H., Marrs, G.L., Gouvion, C.M., Lee, G., Davidson, B.L., Paulson, H.L., Allele-specific silencing of dominant disease genes. Proc. Natl. Acad. Sci. USA 100 (2003), 7195–7200.
42. Nakanishi, K., Weinberg, D.E., Bartel, D.P., Patel, D.J., Structure of yeast Argonaute with guide RNA. Nature 486 (2012), 368–374.
43. Nakanishi, K., Ascano, M., Gogakos, T., Ishibe-Murakami, S., Serganov, A.A., Briskin, D., Morozov, P., Tuschl, T., Patel, D.J., Eukaryote-specific insertion elements control human ARGONAUTE slicer activity. Cell Rep. 3 (2013), 1893–1900.
44. Ohnishi, Y., Tamura, Y., Yoshida, M., Tokunaga, K., Hohjoh, H., Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi. PLoS ONE, 3, 2008, e2248.
45. Østergaard, M.E., Southwell, A.L., Kordasiewicz, H., Watt, A.T., Skotte, N.H., Doty, C.N., Vaid, K., Villanueva, E.B., Swayze, E.E., Bennett, C.F., et al. Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Res. 41 (2013), 9634–9650.
46. Paez-Espino, D., Sharon, I., Morovic, W., Stahl, B., Thomas, B.C., Barrangou, R., Banfield, J.F., CRISPR immunity drives rapid phage genome evolution in Streptococcus thermophilus. MBio, 6, 2015, e00262-15.
47. Pattanayak, V., Ramirez, C.L., Joung, J.K., Liu, D.R., Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection. Nat. Methods 8 (2011), 765–770.
48. Pedersen, L., Hagedorn, P.H., Lindholm, M.W., Lindow, M., A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent. Mol. Ther. Nucleic Acids, 3, 2014, e149.
49. Pfister, E.L., Kennington, L., Straubhaar, J., Wagh, S., Liu, W., DiFiglia, M., Landwehrmeyer, B., Vonsattel, J.-P., Zamore, P.D., Aronin, N., Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. Curr. Biol. 19 (2009), 774–778.
50. Ran, F.A., Hsu, P.D., Lin, C.-Y., Gootenberg, J.S., Konermann, S., Trevino, A.E., Scott, D.A., Inoue, A., Matoba, S., Zhang, Y., Zhang, F., Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154 (2013), 1380–1389.
51. Richardson, C.D., Ray, G.J., DeWitt, M.A., Curie, G.L., Corn, J.E., Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA. Nat. Biotechnol. 34 (2016), 339–344.
52. Salomon, W.E., Jolly, S.M., Moore, M.J., Zamore, P.D., Serebrov, V., Single-molecule imaging reveals that argonaute reshapes the binding properties of its nucleic acid guides. Cell 162 (2015), 84–95.
53. Schirle, N.T., MacRae, I.J., The crystal structure of human Argonaute2. Science 336 (2012), 1037–1040.
54. Schirle, N.T., Sheu-Gruttadauria, J., MacRae, I.J., Structural basis for microRNA targeting. Science 346 (2014), 608–613.
55. Schwarz, D.S., Hutvágner, G., Du, T., Xu, Z., Aronin, N., Zamore, P.D., Asymmetry in the assembly of the RNAi enzyme complex. Cell 115 (2003), 199–208.
56. Schwarz, D.S., Ding, H., Kennington, L., Moore, J.T., Schelter, J., Burchard, J., Linsley, P.S., Aronin, N., Xu, Z., Zamore, P.D., Designing siRNA that distinguish between genes that differ by a single nucleotide. PLoS Genet., 2, 2006, e140.
57. Singh, D., Sternberg, S.H., Fei, J., Doudna, J.A., Ha, T., Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9. Nat. Commun., 7, 2016, 12778.
58. Slaymaker, I.M., Gao, L., Zetsche, B., Scott, D.A., Yan, W.X., Zhang, F., Rationally engineered Cas9 nucleases with improved specificity. Science 351 (2016), 84–88.
59. Sternberg, S.H., Redding, S., Jinek, M., Greene, E.C., Doudna, J.A., DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature 507 (2014), 62–67.
60. Sternberg, S.H., LaFrance, B., Kaplan, M., Doudna, J.A., Conformational control of DNA target cleavage by CRISPR-Cas9. Nature 527 (2015), 110–113.
61. Sugimoto, N., Nakano, S., Katoh, M., Matsumura, A., Nakamuta, H., Ohmichi, T., Yoneyama, M., Sasaki, M., Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes. Biochemistry 34 (1995), 11211–11216.
62. Sullenger, B.A., Nair, S., From the RNA world to the clinic. Science 352 (2016), 1417–1420.
63. Sun, C.L., Barrangou, R., Thomas, B.C., Horvath, P., Fremaux, C., Banfield, J.F., Phage mutations in response to CRISPR diversification in a bacterial population. Environ. Microbiol. 15 (2013), 463–470.
64. Szczelkun, M.D., Tikhomirova, M.S., Sinkunas, T., Gasiunas, G., Karvelis, T., Pschera, P., Siksnys, V., Seidel, R., Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes. Proc. Natl. Acad. Sci. USA 111 (2014), 9798–9803.
65. Tsai, S.Q., Joung, J.K., Defining and improving the genome-wide specificities of CRISPR-Cas9 nucleases. Nat. Rev. Genet. 17 (2016), 300–312.
66. Tsai, S.Q., Wyvekens, N., Khayter, C., Foden, J.A., Thapar, V., Reyon, D., Goodwin, M.J., Aryee, M.J., Joung, J.K., Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat. Biotechnol. 32 (2014), 569–576.
67. Tsai, S.Q., Zheng, Z., Nguyen, N.T., Liebers, M., Topkar, V.V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A.J., Le, L.P., et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33 (2015), 187–197.
68. Ui-Tei, K., Naito, Y., Nishi, K., Juni, A., Saigo, K., Thermodynamic stability and Watson-Crick base pairing in the seed duplex are major determinants of the efficiency of the siRNA-based off-target effect. Nucleic Acids Res. 36 (2008), 7100–7109.
69. Ui-Tei, K., Naito, Y., Zenno, S., Nishi, K., Yamato, K., Takahashi, F., Juni, A., Saigo, K., Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Res. 36 (2008), 2136–2151.
70. Vaish, N., Chen, F., Seth, S., Fosnaugh, K., Liu, Y., Adami, R., Brown, T., Chen, Y., Harvie, P., Johns, R., et al. Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs. Nucleic Acids Res. 39 (2011), 1823–1832.
71. Wang, X.H., Aliyari, R., Li, W.X., Li, H.W., Kim, K., Carthew, R., Atkinson, P., Ding, S.W., RNA interference directs innate immunity against viruses in adult Drosophila. Science 312 (2006), 452–454.
72. Wang, H., La Russa, M., Qi, L.S., CRISPR/Cas9 in Genome Editing and Beyond. Annu. Rev. Biochem. 85 (2016), 227–264.
73. Wee, L.M., Flores-Jasso, C.F., Salomon, W.E., Zamore, P.D., Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties. Cell 151 (2012), 1055–1067.
74. Wittrup, A., Lieberman, J., Knocking down disease: a progress report on siRNA therapeutics. Nat. Rev. Genet. 16 (2015), 543–552.
75. Wyvekens, N., Topkar, V.V., Khayter, C., Joung, J.K., Tsai, S.Q., Dimeric CRISPR RNA-Guided FokI-dCas9 Nucleases Directed by Truncated gRNAs for Highly Specific Genome Editing. Hum. Gene Ther. 26 (2015), 425–431.
76. Xiong, X., Chen, M., Lim, W.A., Zhao, D., Qi, L.S., CRISPR/Cas9 for Human Genome Engineering and Disease Research. Annu. Rev. Genomics Hum. Genet. 17 (2016), 131–154.
77. Yu, D., Pendergraff, H., Liu, J., Kordasiewicz, H.B., Cleveland, D.W., Swayze, E.E., Lima, W.F., Crooke, S.T., Prakash, T.P., Corey, D.R., Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 150 (2012), 895–908.