The structure, function and application of the hammerhead ribozyme

European Journal of Biochemistry

Volumn 245, Issue 1, 1997, Pages 1-16

  Birikh, Klara R ^a   Heaton, Paul A ^a   Eckstein, Fritz ^a  

^a MAX PLANCK INSTITUTE OF EXPERIMENTAL MEDICINE   (Germany)

Author keywords

Catalytic RNA; Delivery; Design; Gene inhibition; Mechanism

Indexed keywords

DRUG CARRIER; LIPOSOME; RIBOZYME; VIRUS VECTOR;

CATALYSIS; DRUG BINDING; DRUG DESIGN; DRUG FORMULATION; DRUG SYNTHESIS; DRUG TARGETING; ENZYME KINETICS; ENZYME MECHANISM; ENZYME METABOLISM; ENZYME SPECIFICITY; GENE EXPRESSION REGULATION; GENE TRANSFER; HUMAN; IN VITRO STUDY; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; REVIEW; RNA CLEAVAGE; RNA METABOLISM; RNA STRUCTURE; TRANSGENIC ANIMAL;

ANIMALIA;

EID: 0030939002     PISSN: 00142956     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1432-1033.1997.t01-3-00001.x     Document Type: Review

References (171)

1. Ali, M., Lemoine, N. R. & Ring, C. J. A. (1994) The use of DNA viruses as vectors for gene therapy, Gene Ther. 1, 367-384.
2. Altman, S. (1990) Ribonuclease P, J. Biol. Chem. 265, 20053-20056.
3. Amiri, K. M. A. & Hagerman, P. J. (1994) Global conformation of a self-cleaving hammerhead RNA, Biochemistry 33, 13 172-13 177.
4. Amiri, K. M. A. & Hagerman, P. J. (1996) The global conformation of an active hammerhead RNA during the process of self-cleavage, J. Mol. Biol. 261, 125-134.
5. Amontov, S. V. & Taira, K. (1996) Hammerhead minizymes with high cleavage activity: a dimeric structure as the active conformation of minizymes, J. Am. Chem. Soc. 118, 1624-1628.
6. Baier, G., Coggeshall, K. M., Baier-Bitterlich, G., Giampa, L., Telford, D., Herbert, E., Shin, W. & Altman, A. (1994) Construction and characterisation of lck- and fyn-specific tRNA:ribozyme chimeras, Mol. Immunol. 31, 923-932.
7. Bassi, G. S., Mollegaard, N. E., Murchie, A. I. H., von Kitzing, E. & Lilley, D. M. J. (1995) Ionic interactions and the global conformations of the hammerhead ribozyme, Nat. Struct. Biol. 2, 45-55.
8. Bassi, G. S., Murchie, A. I. H. & Lilley, D. M. J. (1996) The ion-induced folding of the hammerhead ribozyme: core sequence changes that preturb folding into the inactive conformation, RNA 2, 756-768.
9. Beck, J. & Nassal, M. (1995) Efficient hammerhead ribozyme-mediated cleavage of the structured hepatitis B virus encapsidation signal in vitro and in cell extracts, but not in intact cells, Nucleic Acids Res. 23, 4954-4962.
10. Beigelman, L., McSwiggen, J. A., Draper, K. G., Gonzalez, C., Jensen, K., Karpeisky, A. M., Modak, A. S., Matulic-Adamic, J., DiRenzo, A. B., Haeberli, P., Sweedler, D., Tracz, D., Grimm, S., Wincott, F., Thackray, V. G. & Usmann, N. (1995) Chemical modification of hammerhead ribozymes: catalytic activity and nuclease resistance, J. Biol. Chem. 270, 25702-25708.
11. Benseler, F., Fu, D.-J., Ludwig, J. & McLaughlin, L. W. (1993) Hammerhead-like molecules containing non-nucleoside linkers are active RNA catalysts, J. Am. Chem. Soc. 115, 8483-8484.
12. Bertrand, E. L. & Rossi, J. J. (1994) Facilitation of hammerhead ribozyme catalysis by the nucleocapsid protein of HIV-1 and the heterogeneous nuclear ribonucleoprotein A1, EMBO J. 13, 2904-2912.
13. Bertrand, E. & Rossi, J. (1996) Anti-HIV therapeutic hammerhead ribozymes: targeting strategies and optimization of intracellular function, Nucleic Acids Mol. Biol. 10, 301-314.
14. Bertrand, E., Pictet, R. & Grange, T. (1994) Can hammerhead ribozymes be efficient tools to inactivate gene function? Nucleic Acids Res. 22, 293-300.
15. Birikh, K. R., Berlin, Y. A., Soreq, H. & Eckstein, F. (1997) Probing accessible sites for ribozyme on human acetylcholinesterase RNA, RNA, in the press.
16. Burgin, A. B., Gonzalez, C., Matulic-Adamic, J., Karpeisky, A. M., Usman, N., McSwiggen, J. A. & Beigelman, L. (1996) Chemically modified hammerhead ribozymes with improved catalytic rates, Biochemistry 35, 14090-14097.
17. Cech, T. R. (1990) Self-splicing of group I introns, Annu. Rev. Biochem. 59, 543-568.
18. Chapman, K. B. & Szostak, J. W. (1994) In vitro selection of catalytic RNAs, Curr. Opin. Struct. Biol. 4, 618-622.
19. Chatterjee, S., Johnson, P. R. & Wong, K. K. (1992) Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector, Science 258, 1485-1488.
20. Chowrira, B. M., Pavco, P. A. & McSwiggen, J. A. (1994) In vitro and in vivo comparison of hammerhead, hairpin, and hepatitus delta virus self-processing ribozyme cassettes, J. Biol. Chem. 269, 25865-25864.
21. Christoffersen, R. E., McSwiggen, J. & Konings, D. (1994) Application of computational technologies to ribozyme biotechnology products, J. Mol. Struct. (Theochem) 311, 273-284.
22. Clouet-D'Orval, B. & Uhlenbeck, O. C. (1996) Kinetic characterisation of I/II format hammerhead ribozymes, RNA 2, 483-491.
23. Cotten, M. & Birnstiel, M. L. (1989) Ribozyme mediated destruction of RNA in vivo, EMBO J. 8, 3861-3866.
24. Craig, M. E., Crothers, D. M. & Doty, P. (1971) Relaxation kinetics of dimer formation by self complementary oligonucleotides, J. Mol. Biol. 62, 383-401.
25. Crisell, P., Thompson, S. & James, W. (1993) Inhibition of HIV-1 replication by ribozymes that show poor activity in vitro, Nucleic Acids Res. 21, 5251-5255.
26. Dahm, S. C. & Uhlenbeck, O. C. (1991) Role of divalent metal ions in the hammerhead RNA cleavage reaction, Biochemistry 30, 9464-9469.
27. Dahm, S. C., Derrick, W. B. & Uhlenbeck, O. C. (1993) Evidence for the role of solvated metal hydroxide in the hammerhead cleavage mechanism, Biochemistry 32, 13040-13045.
28. de-Feyter R., Young, M., Schroeder, K., Dennis, E. S. & Gerlach, W. (1996) A ribozyme gene and an antisense gene are equally effective in conferring resistance to tobacco mosaic virus on transgenic tobacco, Mol. Gen. Genet. 250, 329-338.
29. Denmann, R., Smedman, M., Ju, W., Rubenstein, R., Potempska, A. & Miller, D. L. (1994) Ribozyme mediated degradation of β-amiloid peptide precursor mRNA in COS-7 cells, Nucleic Acids Res. 22, 2375-2382.
30. Ding, D. & Lipshitz, N. D. (1993) Localized RNAs and their functions, Bioessays 15, 651-658.
31. Dropulic, B. & Jeang, K. T. (1994) Intracellular susceptibility to ribozymes in a tethered substrate-ribozyme provirus model is not predicted by secondary structures of human immunodeficiency virus type 1 RNAs in vitro, Antisense Res. Dev. 4, 217-221.
32. Dropulic, B., Lin, N. H., Martin, M. A. & Jeang, K. T. (1992) Functional characterization of a U5 ribozyme: Intracellular suppression of human immunodeficiency virus type 1 expression, J. Virol. 66, 1432-1441.
33. Efrat, S., Leiser, M., Wu, Y. J., Fuscodemane, D., Emran, O. A., Surana, M., Jetton, T. L., Magnuson, M. A., Weir, G. & Fleischer, N. (1994) Ribozyme-mediated attenuation of pancreatic β-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion, Proc. Natl Acad. Sci. USA 91, 2051-2055.
34. Ellis, J. & Rogers, J. (1993) Design and specificity of hammerhead ribozymes against calretinin mRNA, Nucleic Acids Res. 21, 5171-5178.
35. Fedor, M. J. & Uhlenbeck, O. C. (1990) Substrate sequence effects on 'hammerhead' RNA catalytic efficiency, Proc. Natl Acad. Sci. USA 87, 1668-1672.
36. Fedor, M. J. & Uhlenbeck, O. C. (1992) Kinetics of intermolecular cleavage by hammerhead ribozymes, Biochemistry 31, 12042-12054.
37. Feng, M., Cabrera, G., Deshane. J., Scanlon, K. J. & Curiel, D. T. (1995) Neoplastic reversion accomplished by high efficiency adenoviral-mediated delivery of an anti-ras ribozyme, Cancer Res. 55, 2024-2028.
38. Ferbeyre, G., Bratty, J., Chen, H. & Cedergren, R. (1996) Cell cycle arrest promotes trans-hammerhead ribozyme action in yeast, J. Biol. Chem. 271, 19318-19323.
39. Fersht, A. (1977) Enzyme structure and mechanism, W. H. Freeman and Company, Reading.
40. Flory, C. M., Pavco, P. A., Jarvis, T. C., Lesch, M. E., Wincott, F. E., Beigelman, L., Hunt, S. W. & Schrier, D. J. (1996) Nuclease-resistant ribozymes decrease stromelysin mRNA levels in rabbit synovium following exogenous delivery to the knee joint, Proc. Natl Acad. Sci. USA 93, 754-758.
41. Fu, D. J., Benseler, F. & McLaughlin, L. W. (1994) Hammerhead ribozymes containing non-nucleoside linkers are active RNA catalysts, J. Am. Chem. Soc. 116, 4591-4598.
42. Fuerst, T. R., Niles, E. G., Studier, F. W. & Moss, B. (1986) Eukariotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase, Proc. Natl Acad. Sci. USA 83, 8122-8126.
43. Funato, T., Shitara, T., Tone, T., Jiao, L., Kashani-Sabet, M. & Scanlon, K. J. (1994) Suppression of H-ras-mediated transformation in NIH3T3 cells by a ras ribozyme, Biochem. Pharmacol. 48, 1471-1475.
44. Gold, L., Polisky, B., Uhlenbeck, O. & Yarus, M. (1995) Diversity of oligonucleotide functions, Annu. Rev. Biochem. 64, 763-797.
45. Gregoriadis, G. (1995) Engineering liposomes for drug delivery: progress ang problems, Trends Biotechnol. 13, 527-537.
46. Haseloff, J. & Gerlach, W. L. (1988) Simple RNA enzymes with new and highly specific endoribonuclease activity, Nature 334, 585-591.
47. Heidenreich, O. & Eckstein, F. (1992) Hammerhead ribozyme-mediated cleavage of the long terminal repeat of human immunodeficiency virus type 1, J. Biol. Chem. 267, 1904-1909.
48. Heidenreich, O. & Eckstein, F. (1997) Synthetic ribozymes: The hammerhead ribozyme, in Concepts in gene therapy (Strauss, M. & Barranger, J., eds) in the press, Walter de Gruyter, Berlin.
49. Heidenreich, O., Benseler, F., Fahrenholz, A. & Eckstein, F. (1994) High activity and stability of hammerhead ribozymes containing 2′-modified pyrimidine nucleosides and phosphorothioates, J. Biol. Chem. 269, 2131-2138.
50. Heidenreich, O., Kang, S.-H., Brown, D. A., Xu, X., Swiderski, P., Rossi, J. J., Eckstein, F. & Nerenberg, M. (1995) Ribozyme-mediated RNA degradation in nuclei suspension, Nucleic Acids Res. 2223-2228.
51. Heidenreich, O., Xu, X. & Nerenberg, M. (1996a) A hammerhead ribozyme cleaves its target RNA during RNA preparation, Antisense Nucleic Acid Drug Dev. 6, 141-144.
52. Heidenreich, O., Xu, X., Swiderski, P & Nerenberg, M. (1996b) Correlation of activity with stability of chemically modified ribozymes in nuclei suspension, Antisense Nucleic Acid Drug Dev. 6, 111-118.
53. Heinrich, J. C., Tabler, M. & Louis, C. (1993) Attenuation of white gene-expression in transgenic Drosophila melanogaster: possible role of a catalytic antisense RNA, Dev. Genet. 14, 258-265.
54. Heinrich, J. C., Tabler, M. & Louis, C. (1995) Influence of chromosomal position and copy number of a white-directed ribozyme gene on the suppression of eye pigmentation in drosophila melanogaster, Antisense Res. Dev. 5, 155-160.
55. Hendrix, C., Anne, J., Joris, B., Van Aerschot, A. & Herdewijn, P. (1996) Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA, Biochem. J. 314, 655-661.
56. Hendry, P. & McCall, M. (1996) Unexpected anisotropy in substrate cleavage rates by asymmetric hammerhead ribozymes, Nucleic Acids Res. 24, 2679-2684.
57. Hendry, P., McCall, M. J., Santiago, F. S. & Jennings, P. A. (1995) In vitro activity of minimised hammerhead ribozymes, Nucleic Acids Res. 23, 3922-3927.
58. Herschlag, D. (1991) Implications of ribozyme kinetics for targeting the cleavage of specific RNA molecules in vivo: more isn't always better, Proc. Natl Acad. Sci. USA 88, 6921-6925.
59. Herschlag, D. (1995) RNA chaperones and the RNA folding problem, J. Biol. Chem. 270, 20871-20874.
60. Herschlag, D., Khosla, M., Tsuchihashi, Z. & Karpel, R. L. (1994) An RNA chaperone activity of non-specific RNA binding proteins in hammerhead ribozyme catalysis, EMBO J. 13, 2913-2924.
61. Hertel, K. J., Herschlag, D. & Uhlenbeck, O. C. (1994) A kinetic and thermodynamic framework for the hammerhead ribozyme reaction, Biochemistry 33, 3374-3385.
62. Hertel, K. J., Herschlag, D. & Uhlenbeck, O. C. (1996) Specificity of hammerhead ribozyme cleavage, EMBO J. 15, 3751-3757.
63. Hertel, K. J., Pardi, A., Uhlenbeck, O. C., Koizumi, M., Ohtsuka, E., Uesugi, S., Cedergren, R., Eckstein, F., Gerlach, W. L., Hodgson, R. & Symons, R. H. (1992) Numbering system for the hammerhead ribozyme, Nucleic Acids Res. 20, 3252.
64. Ho, S. P., Britton, D. H. O., Stone, B. A., Behrens, D. L., Leffet, L. M., Hobbs, F. W., Miller, J. A. & Trainor, G. L. (1996) Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries, Nucleic Acids Res. 24, 1901-1907.
65. Homann, M., Tabler, M., Tzortzakaki, S. & Sczakiel, G. (1994) Extension of helix II of an HIV-1-directed hammerhead ribozyme with long antisense flanks does not alter kinetic parameters in vitro but causes loss of the inhibitory potential in living cells, Nucleic Acids Res. 22, 3951-3957.
66. Iverson, B. L. (1995) Ribozymes, recognition and evolution, Chem. Biol. 2, 67-70.
67. Jarvis, T. C., Alby, J. A., Beaudry, A. A., Wincott, F. E., Beigelman, L., McSwiggen, J. A., Usman, N. & Stinchcomb, D. T. (1996) Inhibition of vascular smooth muscle cell proliferation by ribozymes that cleave c-myb mRNA, RNA 2, 419-428.
68. Jeffries, A. C. & Symons, R. H. (1989) A catalytic 13-mer ribozyme, Nucleic Acids Res. 17, 1371-1377.
69. Jucker, F. M. & Pardi, A. (1995) GNRA tetraloops make a U-turn, RNA 1, 219-222.
70. Kashani-Sabet, M., Funato, T., Florenes, V. A., Fodstad, O. & Scanlon, K. J. (1994) Suppression of the neoplastic phenotype in vivo by an anti-ras ribozyme, Cancer Res. 54, 900-902.
71. Kawasaki, H., Ohkawa, J., Tanishige, N., Yoshinari, K., Murata, T., Yokoyama, K. K. & Taira, K. (1996) Selection of the best target site for ribozyme-mediated cleavage within a fusion gene for adenovirus E1A-associated 300 kDa protein (p300) and luciferase, Nucleic Acids Res. 24, 3010-3016.
72. Keese, P., Bruening, G. & Symons, R. H. (1983) Comparative sequence and structure of circular RNAs from two isolates of lucerne transient streak virus, FEBS Lett. 159, 185-190.
73. Kiehntopf, M., Brach, M. A., Licht, T., Petschauer, S., Karawajew, L., Kirschning, C. & Herrmann, F. (1994) Ribozyme-mediated cleavage of the MDR-1 transcript restores chemosensitivity in previously resistant cancer-cells, EMBO J. 13, 4645-4652.
74. Kiehntopf, M., Esquivel, E. L., Brach, M. A. & Herrmann, F. (1995) Ribozymes: Biology, biochemistry, and implications for clinical medicine, J. Mol. Med. 73, 65-71.
75. Kisich, K. O., Stecha, P. F., Harter, H. A. & Stinchcomb, D. T. (1995) Inhibition of TNF-alpha secretion by murine macrophages following in vivo and in vitro ribozyme treatment, J. Cell. Biochem. 19A, 221.
76. 2+ binding, Biochemistry 30, 5145-5150.
77. Kronenwett, R., Haas, R. & Sczakiel, G. (1996) Kinetic selectivity of complementary nucleic acids: bcr-abl-directed antisense RNA and ribozymes, J. Mol. Biol. 259, 632-644.
78. Kuimelis, R. G. & McLaughlin, L. W. (1995) Hammerhead ribozyme-mediated cleavage of a substrate containing an internucleotide bridging 5′-phosphorothioate: Implications for the cleavage mechanism and the catalytic role of the metal co-factor, J. Am. Chem. Soc. 117, 11019-11020.
79. Kuimelis, R. G. & McLaughlin, L. W. (1996a) Probing the cleavage activity of the hammerhead ribozyme using analog complexes, Nucleic Acids Mol. Biol. 10, 197-216.
80. Kuimelis, R. G. & McLaughlin, L. W. (1996b) Ribozyme-mediated cleavage of a substrate analogue containing an internucleotide-bridging 5′-phosphorothioate - evidence for the single-metal model, Biochemistry 35, 5308-5317.
81. Kumar, P. K. R. & Ellington, A. D. (1995) Artificial evolution and natural ribozymes, FASEB J. 9, 1183-1195.
82. Kumar, P. K. R., Zhou, D. M., Yoshinari, K. & Taira, K. (1996) Mechanistic studies on hammerhead ribozymes, Nucleic Acids Mok. Biol. 10, 217-230.
83. Kuwabara, T., Amontov, S. V., Warashina, M., Ohkawa, J. & Taira, K. (1996) Characterization of several kinds of dimer minizyme: simultaneous cleavage at two sites in HIV-1 tat mRNA by dimer minizymes, Nucleic Acids Res. 24, 2302-2310.
84. L'Huillier, P. J. (1996) Efficacy of hammerhead ribozymes targeting α-lactalbumin transcripts: experiments in cells and transgenic mice, Nucleic Acids Mol. Biol. 10, 283-300.
85. L'Huillier, P. J., Davis, S. R. & Bellamy, A. R. (1992) Cytoplasmic delivery of ribozymes leads to efficient reduction in alpha-lactalbumin mRNA levels in C127I mouse cells, EMBO J. 11, 4411-4418.
86. L'Huillier, P. J. S. S., Stinnakre, M.-G., Lepourry, L., Davis, S. R., Mercier, J.-C. & Vilotte, J.-L. (1996) Efficient and specific ribozyme-mediated reduction of bovine alpha-lactalbumin expression in double transgenic mice, Proc. Natl Acad. Sci. USA 93, 6698-6703.
87. Larsson, S., Hotchkiss, G., Andäng, M., Nyholm, T., Inzunza, J., Jansson, I. & Ährlund-Richter, L. (1994) Reduced β2-microglobulin mRNA levels in transgenic mice expressing a designed hammerhead ribozyme, Nucleic Acids Res. 22, 2242-2248.
88. Lasic, D. D. & Papahadjopoulos, D. (1995) Liposomes revisited, Science 267, 1275-1276.
89. Leonetti, J. P., Degols, G., Clarenc, J. P., Mechti, N. & Lebleu, B. (1993) Cell delivery and mechanism of action of antisense oligonucleotides, Prog. Nucleic Acids Res. 44, 143-166
90. Leopold, H. L., Shore, S. K., Newkirk, T. A., Reddy, R. M. & Reddy, E. P. (1995) Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias, Blood 85, 2162-2170.
91. Lewis, J. G., Lin, K.-J., Kothavale, A., Flanagan, W. M., Matteucci, M. D., DePrince, R. B., Mook, R. A., Hendren, R. W. & Wagner, R. W. (1996) A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA, Proc. Natl Acad. Sci. USA 93, 3176-3181.
92. Lieber, A. & Strauss, M. (1995) Selection of efficient cleavage sites in target RNAs by using a ribozyme expression library, Mol. Cell. Biol. 15, 540-551.
93. Lieber, A. & Kay, M. A. (1996) Adenovirus-mediated expression of ribozymes in mice, J. Virol. 70, 3153-3158.
94. Lyngstdaas, S. P., Risnes, S., Sproat, B. S., Thrane, P. S. & Prydz, H. P. (1995) A synthetic, chemically modified ribozyme eliminates amelogenin, the major translation product in developing mouse enamel in vivo, EMBO J. 14, 5224-5229.
95. Marschall, P. (1996) Inhibition der Genexprexsion mit Ribozymen, Dissertation, Universität Göttingen.
96. Marschall, P., Thomson, J. B. & Eckstein, F. (1994) Inhibition of gene expression with ribozymes, Cell. Mol. Neurobiol. 14, 523-538.
97. McKay, D. B. (1996) Structure and function of the hammerhead ribozyme: an unfinished story, RNA 2, 395-403.
98. 2+-dependent connformational changes in the hammerhead ribozyme, Biochemistry 35, 14710-14716.
99. Michienci, A., Prislei, S. & Bozzoni, I. (1996) U1 small nuclear RNA chimeric ribozyme with substrate specificity for the Rev-mRNA of human immunodeficiency virus. Proc. Natl Acad. Sci. USA 93, 7219-7224.
100. Miller, W. A., Hercus, T., Waterhouse, P. M. & Gerlach, W. L. (1991) A satellite RNA of barley yellow dwarf virus contains a novel hammerhead structure in the self-cleaving domain, Virology 183, 711-720.
101. Müller, G., Strack, B., Dannull, J., Sproat, B. S., Surovoy, A., Jung, G. & Moelling, K. (1994) Amino acid requirements of the nucleo-capsid protein of HIV-1 for increasing catalytic activity of a Ki-ras ribozyme in vitro, J. Mol. Biol. 242, 422-429.
102. Murray, J. B., Adams, C. J., Arnold, J. R. P. & Stockley, P. G. (1995) The roles of the conserved pyrimidine bases in hammerhead ribozyme catalysis - evidence for a magnesium ion-binding site, Biochem. J. 311, 487-494.
103. Nakamaye, K. L. & Eckstein, F. (1994) AUA-Cleaving hammerhead ribozymes: Attempted selection for improved cleavage, Biochemistry 33, 1271-1277.
104. Narlikar, G. J. & Herschlag, D. (1997) Mechanistic aspects of enzymatic catalysis: lessons from comparision of RNA and protein enzymes, Annu. Rev. Biochem., in the press.
105. Nelson, J. W. & Tinoco, I. Jr (1982) Comparison of the kinetics of ribooligonucleotide, deoxyribo-oligonucleotide, and hybrid oligonucleotide double-strand formation by temperature-jump kinetics, Biochemistry 21, 5289-5295.
106. Odai, O., Hiroaki, H., Tanaka, T. & Uesugi, S. (1994) Properties of a hammerhead-type RNA enzyme system that consists of 3 three RNA oligomer strands, Nucleosides & Nucleotides 13, 1569-1579.
107. Ohkawa, J., Yuyama, N., Takebe, Y., Nishikawa, S. & Taira, K. (1993) Importance of independence in ribozyme reactions: Kinetic behavior of trimmed and of simply connected multiple ribozymes with potential activity against human immunodeficiency virus, Proc. Natl Acad. Sci. USA 90, 11302-11306.
108. Ohkawa, J., Koguma, T., Kohda, T. & Taira, K. (1995) Ribozymes: from mechanistic studies to applications in vivo, J. Biochem. 118, 251-258.
109. Ohta, Y., Kijima, H., Ohkawa, T., Kashani-Sabet, M. & Scanlon, K. (1996) Tissue-specific expression of an anti-ras ribozyme inhibits proliferation of human malignant melanoma cells, Nucleic Acids Res. 24, 938-942.
110. Pachuk, C. J., Yoon, K., Moelling, K. & Coney, L. R. (1994) Selective cleavage of bcr-abl chimeric RNAs by a ribozyme targeted to non-contigous sequences, Nucleic Acids Res. 22, 301-307.
111. Peracchi, A., Beigelman, L., Usman, N. & Herschlag, D. (1996) Rescue of abasic hammerhead ribozymes by specific bases added in trans, Proc. Natl Acad. Sci. USA 93, 11522-11527.
112. Perriman, R., Delves, A. & Gerlach, W. L. (1992) Extended target-site specificity for a hammerhead ribozyme, Gene (Amst.) 113, 157-163.
113. Perriman, R., Breuning, G., Dennis, E. S. & Peacock, W. J. (1995) Effective ribozyme delivery in plant cells, Proc. Natl Acad. Sci. USA 92, 6175-6179.
114. Piccirilli, J. A., Vyle, J. S., Caruthers, M. H. & Cech, T. R. (1993) Metal ion catalysis in the Tetrahymena ribozyme reaction, Nature 361, 85-88.
115. Pieken, W. A., Olsen, D. B., Benseler, R, Aurup, H. & Eckstein, F. (1991) Kinetic characterization of ribonuclease-resistant 2′-modified hammerhead ribozymes, Science 253, 314-317.
116. Pley, H. W., Flaherty, K. M. & McKay, D. B. (1994) Three-dimensional structure of a hammerhead ribozyme, Nature 372, 68-74.
117. Pörschke, D. & Eigen, M. (1971) Co-operative non-enzymatic base recognition, J. Mol. Biol. 62, 361-381.
118. Pörschke, D., Uhlenbeck, O. C. & Martin, F. H. (1973) Thermodynamics and kinetics of the helix-coil transition of oligomers containing GC base pairs, Biopolymers 12, 1313-1335.
119. n, Nucleic Acids Res. 1, 109-127.
120. Rittner, K., Burmester, C. & Sczakiel, G. (1993) in vitro selection of fast-hybridizing and effective antisense RNAs directed against the human immunodeficiency virus type I, Nucleic Adds Res. 21, 1381-1387.
121. Romani, A. & Scarpa, A. (1992) Regulation of cell magnesium, Arch. Biochem. Biophys. 298, 1-12.
122. Rossi, J. J. (1995) Controlled, targeted, intracellular expression of ribozymes: progress and problems, Trends Biotechnol. 13, 301-306.
123. Ruffner, D. E., Stormo, G. D. & Uhlenbeck, O. C. (1990) Sequence requirements of the hammerhead RNA self-cleavage reaction, Biochemistry 29, 10695-10702.
124. Sawata, S., Komiyama, M. & Taira, K. (1995) Kinetic evidence based on solvent isotope effects for the nonexistence of a proton-transfer process in reactions catalyzed by a hammerhead ribozyme - implication to the double-metal-ion mechanism of catalysis, J. Am. Chem. Soc. 117, 2357-2358.
125. Scott, W. G., Finch, J. T. & Klug, A. (1995) The crystal structure of an all-RNA hammerhead ribozyme - a proposed mechanism for RNA catalytic cleavage, Cell 81, 991-1002.
126. Sczakiel, G. (1996) Hammerhead ribozymes with long flanking sequences: a structural and kinetic view, Nucleic Acids Mol. Biol. 10, 231-242.
127. Sczakiel, G. & Goody, R. S. (1994) Antisense principle or ribozyme action, Biol. Chem. Hoppe-Seyler 375, 745-746.
128. Shimayama, T., Nishikawa, S. & Taira, K. (1995) Generality of the NUX rule - kinetic analysis of the results of systematic mutations in the trinucleotide at the cleavage site of hammerhead ribozymes, Biochemistry 34, 3649-3654.
129. Sigurdsson, S. T., Tuschl, T. & Eckstein, F. (1995) Probing RNA tertiary structure: interhelical cross-linking of the hammerhead ribozyme, RNA 1, 575-583.
130. Sioud, M., Natvig, J. B. & Forre, O. (1992) Preformed ribozyme destroys tumour necrosis factor mRNA in human cells, J. Mol. Biol. 223, 831-835.
131. Sioud, M., Opstadt, A., Zhao, J.-Q., Levitz, R., Benheim, C. & Drlica, K. (1994) In vivo decay parameters of hammerhead ribozymes, Nucleic Acids Res. 22, 5571-5575
132. Slim, G. & Gait, M. J. (1991) Configurationally defined phosphorothioate-containing oligoribonucleotides in the study of the mechanism of cleavage of hammerhead ribozymes, Nucleic Acids Res. 19, 1183-1188.
133. Smith. A. E. (1995) Viral vectors in gene therapy, Annu. Rev. Microbiol. 49, 807-838.
134. Sproat, B. S. (1996) Synthetic catalytic oligonucleotides based on the hammerhead ribozyme, Nucleic Acids Mol. Biol 10, 265-282.
135. Steinecke, P., Steger, G. & Schreier, P. H. (1994) A stable hammerhead structure is not required for endonucleolitic activity of a ribozyme in vivo, Gene 149, 47-54.
136. Sullenger, B. A. & Cech, T. R. (1993) Tethering ribozymes to a retroviral packaging signal for destruction of viral RNA, Science 262, 1566-1569.
137. Sullivan, S. M. (1994) Development of ribozymes for gene-therapy, J. Invest. Dermatol. 103, S85-89.
138. Sun, L. Q., Warrilow, D., Wang, L., Witherington, C., Macpherson, J. & Symonds, G. (1994) Ribozyme-mediated suppression of Moloney murine leukemia virus and human-immunodeficiency-virus type I replication in permissive cell lines, Proc. Natl Acad. Sci. USA 91, 9715-9719.
139. Sun, L. Q., Pyati, J., Smythe, J., Wang, L., Macpherson, J., Gerlach, W. & Symonds, G. (1995a) Resistance to human immunodeficiency virus type 1 infection conferred by transduction of human peripheral blood lymphocytes with ribozyme, antisense, or polymeric trans-activation response element constructs, Proc. Natl Acad. Sci. USA 92, 7272-7276.
140. Sun, L. Q., Wang, L., Gerlach, W. L. & Symonds, G. (1995b) Target sequence-specific inhibition of HIV-1 replication by ribozymes directed to tat RNA, Nucleic Acids Res. 23, 2909-2913.
141. Sun, L.-Q., Gerlach, W. L. & Symonds, G. (1996) The use of ribozymes to inhibit HIV replication, Nucleic Adds Mol. Biol. 10, 329-342.
142. Sweeney, R., Fan, Q. & Yao, M.-C. (1996) Antisense ribosomes: rRNA as a vehicle for antisense RNAs, Proc. Natl Acad. Sci. USA 93, 8518-8523.
143. Symons, R. H. (1992) Small catalytic RNAs, Annu. Rev. Biochem. 61, 641-671.
144. Tabler, M., Homann, M., Tzortzakaki, S. & Sczakiel, G. (1994) A three-nucleotide helix I is sufficient for full activity of a hammerhead ribozyme: advantages of an asymmetric design, Nucleic Acids Res. 22, 3958-3965.
145. Tang, X. B., Hobom, G., & Luo, D. (1994) Ribozyme mediated destruction of influenza A virus in vitro and in vivo, J. Med. Virol. 42, 385-395.
146. Thompson J., Ayers, D. F., Malmstrom, T. A., McKenzie, T. L., Ganousis, L., Chowrira, B. M., Couture, L. & Stinchcomb, D. T. (1995a) Improved accumulation and activity of ribozymes expressed from a tRNA-based RNA polymerase III promoter, Nucleic Acids Res. 23, 2259-2268.
147. Thompson, J. D., Macejak, D., Couture, L. & Stinchcomb, D. T. (1995b) Ribozymes in gene therapy, Nat. Med. 1, 277-278.
148. Thomson, J. B., Tuschl, T. & Eckstein, F. (1993) Activity of hammerhead ribozyme containing non-nucleotidic linkers, Nucleic Acids Res. 21, 5600-5603.
149. Thomson, J. B., Tuschl, T. & Eckstein, F. (1996) The hammerhead ribozyme, Nucleic Acids Mol. Biol. 10, 173-196.
150. Tsuchihashi, Z., Khosla, M. & Herschlag, D. (1993) Protein enhancement of hammerhead ribozyme catalysis, Science 262, 99-102.
151. Tuschl, T. & Eckstein, F. (1993) Hammerhead ribozymes: Importance of stem-loop II for activity, Proc. Natl Acad. Sci. USA 90, 6991-6994.
152. Tuschl, T, Gohlke, C., Jovin, T. M., Westhof, E. & Eckstein, F. (1994) A three-dimensional model for the hammerhead ribozyme based on fluorescence measurements, Science 266, 785-789.
153. Tuschl, T., Thomson, J. B. & Eckstein, F. (1995) RNA cleavage by small catalytic RNAs, Curr. Opin. Struct. Biol. 5, 296-302.
154. Uhlenbeck, O. C. (1987) A small catalytic oligoribonucleotide, Nature 328, 596-600.
155. Usman, N. & Stinchcomb, D. T. (1996) Design, synthesis and function of therapeutic ribozymes, Nucleic Acids Mol. Biol. 10, 243-264.
156. van Tol, H., Buzayan, J. M., Feldstein, P. A., Eckstein, F. & Bruening, G. (1990) Two autolytic processing reactions of a satellite RNA proceed with inversion of configuration, Nucleic Acids Res. 18, 1971-1975.
157. Ventura, M., Wang, P., Ragot, T., Perricaudet, M. & Saragosti, S. (1993) Activation of HIV-specific ribozyme activity by self-cleavage, Nucleic Acids Res. 21, 3249-3255.
158. Wagner, R. & Simons, R. (1994) Antisense RNA control in bacteria, phages, and plasmids, Annu. Rev. Microbiol. 48, 713-742.
159. Werner, M. & Uhlenbeck, O. C. (1995) The effect of base mismatches in the substrate recognition helices of hammerhead ribozymes on binding and catalysis, Nucleic Acids Res. 23, 2092-2096.
160. Westway, S. K., Larson, G. P., Li, S., Zaia, J. A. & Rossi, J. J. (1995) A chimeric tRNA(Lys3)-ribozyme inhibits HIV replication following virion assembly, Nucleic Acids Symp. Ser. 33, 194-199.
161. Woolf, T. M. (1995) To cleave or not to cleave: ribozymes and antisense, Antisense Res. Dev. 5, 227-232.
162. Yuyama, N., Ohkawa, J., Koguma, T., Shirai, M. & Taira, K. (1994) A multifunctional expression vector for an anti-HIV-1 ribozyme that produces a 5′- and 3′-trimmed trans-acting ribozyme, targeted against HIV-1 RNA, and cis-acting ribozymes that are designed to bind to and thereby sequester trans-activator proteins such as Tat and Rev, Nucleic Acids Res. 22, 5060-5067.
163. Zarrinkar, P. P. & Williamsom, J. R. (1996) The kinetic folding pathway of the Tetrahymena ribozyme reveals possible similarities between RNA and protein folding, Nat. Struct. Biol. 3, 432-438.
164. Zhao, J. J. G. & Pick, L. (1993) Generating loss-of-function phenotypes of the fushi tarazu gene with a targeted ribozyme in Drosophila, Nature 365, 448-451.
165. Zhou, C., Bahner, I. C., Larson, G. P., Zaia, J. A., Rossi, J. J. & Kohn, D. B. (1994) Inhibition of HIV-1 in human T-lymphocytes by retrovirally transduced anti-tat and rev hammerhead ribozymes, Gene (Amst.) 149, 33-39.
166. 2+ ion with the pro-R oxygen of the scissile phosphate in the transitionstate of a hammerhead ribozyme-calalysed reaction, J. Am. Chem. Soc. 118, 8969-8970.
167. Zhou, D.-M., Usman, N., Wincott, F. E., Matulic-Adamic, J., Orita, M., Zhang, L.-H., Komiyama, M., Kumar, P. K. R. & Taira, K. (1996b) Evidence for the rate limiting departure of the 5′-oxygen in non-enzymatic and hammerhead ribozyme-catalysed reactions, J. Am. Chem. Soc. 118, 5862-5866.
168. Zhou, C., Bahner, I., Rossi, J. J. & Kohn, D. B. (1996c) Expression of hammerhead ribozyme by retroviral vectors to inhibit HIV-1 replication: comparison of RNA levels and viral inhibition, Antisense Nucleic Acid Drug Dev. 6, 17-24.
169. Zoumadakis, M., Neubert, W. J. & Tabler, M. (1994) The influence of imperfectly paired helices I and II on the catalytic activity of hammerhead ribozymes, Nucleic Acids Res. 22, 5271-5278.
170. Zoumadakis, M. & Tabler, M. (1995) Comparative analysis of cleavage rates after systematic permutation of the NUX-down-arrow consensus target motif for hammerhead ribozymes, Nucleic Acids Res. 23, 1192-1196.
171. Zuker, M. & Stiegler, P. (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information, Nucleic Acids Res. 9, 133-148.