Skip to main content
SpringerLink
Log in

Engineered Catalytic RNA and DNA

New Biochemical Tools for Drug Discovery and Design

  • Technology
  • Published:
American Journal of Pharmacogenomics

Abstract

Since the fundamental discovery that RNA catalyzes critical biological reactions, the conceptual and practical utility of nucleic acid catalysts as molecular therapeutic and diagnostic agents continually develops. RNA and DNA catalysts are particularly attractive tools for drug discovery and design due to their relative ease of synthesis and tractable rational design features. Such catalysts can intervene in cellular or viral gene expression by effectively destroying virtually any target RNA, repairing messenger RNAs derived from mutant genes, or directly disrupting target genes. Consequently, catalytic nucleic acids are apt tools for dissecting gene function and for effecting gene pharmacogenomic strategies. It is in this capacity that RNA and DNA catalysts have been most widely utilized to affect gene expression of medically relevant targets associated with various disease states, where a number of such catalysts are presently being evaluated in clinical trials. Additionally, biotechnological prospects for catalytic nucleic acids are seemingly unlimited. Controllable nucleic acid catalysts, termed allosteric ribozymes or deoxyribozymes, form the basis of effector or ligand-dependent molecular switches and sensors. Allosteric nucleic acid catalysts promise to be useful tools for detecting and scrutinizing the function of specified components of the metabolome, proteome, transcriptome, and genome. The remarkable versatility of nucleic acid catalysis is thus the fountainhead for wide-ranging applications of ribozymes and deoxyribozymes in biomedical and biotechnological research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2
Table II
Fig. 3
Fig. 4

Similar content being viewed by others

Notes

  1. 1The use of tradenames is for product identification purposes only and does not imply endorsement.

References

  1. Meli M, Albert-Fournier B, Maurel MC. Recent findings in the modern RNA world. Int Microbiol 2001; 4: 5–11

    PubMed  CAS  Google Scholar 

  2. Kruger K, Grabowski PJ, Zaug AJ, et al. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 1982; 31: 147–57

    Article  PubMed  CAS  Google Scholar 

  3. Guerrier-Takada C, Gardiner K, Marsh T, et al. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 1983; 35: 849–57

    Article  PubMed  CAS  Google Scholar 

  4. Joyce GF. The antiquity of RNA-based evolution. Nature 2002; 418: 214–21

    Article  PubMed  CAS  Google Scholar 

  5. Newman A. Molecular biology: RNA enzymes for RNA splicing. Nature 2001; 413: 695–6

    Article  PubMed  CAS  Google Scholar 

  6. Moore PB, Steitz TA. The involvement of RNA in ribosome function. Nature 2002; 418: 229–35

    Article  PubMed  CAS  Google Scholar 

  7. Symons RH. Small catalytic RNAs. Annu Rev Biochem 1992; 61: 641–71

    Article  PubMed  CAS  Google Scholar 

  8. Forster AC, Symons RH. Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell 1987; 49: 211–20

    Article  PubMed  CAS  Google Scholar 

  9. Uhlenbeck OC. A small catalytic oligoribonucleotide. Nature 1987; 328: 596–600

    Article  PubMed  CAS  Google Scholar 

  10. Hampel A, Tritz R. RNA catalytic properties of the minimum (–)sTRSV sequence. Biochemistry 1989; 28: 4929–33

    Article  PubMed  CAS  Google Scholar 

  11. Sharmeen L, Kuo MTP, Dinter-Gottlieb G, et al. Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage. J Virol 1988; 62: 2674–9

    PubMed  CAS  Google Scholar 

  12. Saville BJ, Collins RA. A site-specific self-cleavage reaction performed by a novel RNA in neurospora mitochondria. Cell 1990; 61: 685–96

    Article  PubMed  CAS  Google Scholar 

  13. Peebles CL, Perlman PS, Mecklenburg KL, et al. A self-splicing RNA excises an intron lariat. Cell 1986; 44: 213–23

    Article  PubMed  CAS  Google Scholar 

  14. Van der Veen R, Arnberg AC, Van der Horst G, et al. Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro. Cell 1986; 44: 225–34

    Article  PubMed  Google Scholar 

  15. Yean SL, Wuenschell G, Termini J, et al. Met al-ion coordination by U6 small nuclear RNA contributes to catalysis in the spliceosome. Nature 2000; 408: 881–4

    Article  PubMed  CAS  Google Scholar 

  16. Valadkhan S, Manley JL. Splicing-related catalysis by protein-free snRNAs. Nature 2001; 413: 701–7

    Article  PubMed  CAS  Google Scholar 

  17. Noller HF, Hoffarth V, Zimniak L. Unusual resistance of peptidyl transferase to protein extraction procedures. Science 1992; 256: 1416–9

    Article  PubMed  CAS  Google Scholar 

  18. Nissen P, Hansen J, Ban N, et al. The structural basis of ribosome activity in peptide bond synthesis. Science 2000, 930

    Google Scholar 

  19. Cannone JJ, Subramanian S, Schnare MN, et al. The comparative RNA Web (CRW) Site: an online database of comparative sequence and structure information for ribosomal, intron, and other RNAs. BMC Bioinformatics 2002; 3: 2

    Article  PubMed  Google Scholar 

  20. Cech TR. Self-splicing of group I introns. Annu Rev Biochem 1990; 59: 543–68

    Article  PubMed  CAS  Google Scholar 

  21. Bonen L, Vogel J. The ins and outs of group II introns. Trends Genet 2001; 17: 322–31

    Article  PubMed  CAS  Google Scholar 

  22. Newman A. RNA splicing. Curr Biol 1998; 8(25): 903–5

    Article  Google Scholar 

  23. Ban N, Nissen P, Hansen J, et al. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 2000; 289: 905–20

    Article  PubMed  CAS  Google Scholar 

  24. Wimberly BT, Brodersen DE, Clemons WM, et al. Structure of the 30S ribosomal subunit. Nature 2000; 407: 327–39

    Article  PubMed  CAS  Google Scholar 

  25. Yusupov MM, Yusupova GZ, Baucom A, et al. Crystal structure of the ribosome at 5.5 Å resolution. Science 2001; 292: 883–96

    Article  PubMed  CAS  Google Scholar 

  26. Wilson DS, Szostak JW. In vitro selection of functional nucleic acids. Annu Rev Biochem 1999; 68: 611–47

    Article  PubMed  CAS  Google Scholar 

  27. Jaschke A. Artificial ribozymes and deoxyribozymes. Curr Opin Struct Biol 2001; 11: 321–6

    Article  PubMed  CAS  Google Scholar 

  28. Ekland EH, Bartel DP. RNA-catalysed RNA polymerization using nucleoside triphosphates. Nature 1996; 382: 373–6

    Article  PubMed  CAS  Google Scholar 

  29. Johnston WK, Unrau PJ, Lawrence MS, et al. RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension. Science 2001; 292: 1319–25

    Article  PubMed  CAS  Google Scholar 

  30. McGinness KE, Wright MC, Joyce GF. Continuous in vitro evolution of a ribozyme that catalyzes three successive nucleotidyl addition reactions. Chem Biol 2002; 9: 585–96

    Article  PubMed  CAS  Google Scholar 

  31. Tarasow TM, Tarasow SL, Eaton BE. RNA-catalysed carbon-carbon bond formation. Nature 1997; 389: 54–7

    Article  PubMed  CAS  Google Scholar 

  32. Seelig B, Jaschke A. A small catalytic RNA motif with Diels-Alderase activity. Chem Biol 1999; 6: 167–76

    Article  PubMed  CAS  Google Scholar 

  33. Osborne SE, Ellington AD. Nucleic acid selection and the challenge of combinatorial chemistry. Chem Rev 1997; 97: 349–70

    Article  PubMed  CAS  Google Scholar 

  34. Gold L, Polinsky B, Uhlenbeck O, et al. Diversity of oligonucleotide functions. Annu Rev Biochem 1995; 64: 763–97

    Article  PubMed  CAS  Google Scholar 

  35. Breaker RR. In vitro selection of catalytic polynucleotides. Chem Rev 1997; 97: 371–90

    Article  PubMed  CAS  Google Scholar 

  36. Williams KP, Bartel DP. In vitro selection of catalytic RNA. Nucleic Acids Mol Biol 1996; 10: 367–81

    Article  CAS  Google Scholar 

  37. Pan T, Uhlenbeck OC. In vitro selection of RNAs that undergo autolytic cleavage with Pb2+. Biochemistry 1992; 31: 3887–95

    Article  PubMed  CAS  Google Scholar 

  38. Williams KP, Ciafré S, Tocchini-Valentini GP. Selection of novel Mg2+-dependent self-cleaving ribozymes. EMBO J 1995; 14: 4551–7

    PubMed  CAS  Google Scholar 

  39. Jayasena VK, Gold L. In vitro selection of self-cleaving RNAs with a low pH optimum. Proc Natl Acad Sci U S A 1997; 94: 10612–7

    Article  PubMed  CAS  Google Scholar 

  40. Vaish NK, Heaton PA, Fedorova O, et al. In vitro selection of a purine nucleotide-specific hammerhead-like ribozyme. Proc Natl Acad Sci U S A 1998; 95: 2158–62

    Article  PubMed  CAS  Google Scholar 

  41. Tang J, Breaker RR. Structural diversity of self-cleaving ribozymes. Proc Natl Acad Sci U S A 2000; 97: 5784–9

    Article  PubMed  CAS  Google Scholar 

  42. Beaudry A, DeFoe J, Zinnen S, et al. In vitro selection of a novel nuclease-resistant RNA phosphodiesterase. Chem Biol 2000; 7: 323–34

    Article  PubMed  CAS  Google Scholar 

  43. Zinnen SP, Domenico K, Wilson M, et al. Selection, design, and characterization of a new potentially therapeutic ribozyme. RNA 2002; 8: 214–28

    Article  PubMed  CAS  Google Scholar 

  44. Breaker RR, Joyce GF. A DNA enzyme that cleaves RNA. Chem Biol 1994; 1: 223–9

    Article  PubMed  CAS  Google Scholar 

  45. Breaker RR, Joyce GF. A DNA enzyme with Mg2+-dependent RNA phosphoesterase activity. Chem Biol 1995; 2: 655–60

    Article  PubMed  CAS  Google Scholar 

  46. Santoro SW, Joyce GF. A general purpose RNA-cleaving DNA enzyme. Proc Natl Acad Sci U S A 1997; 94: 4262–6

    Article  PubMed  CAS  Google Scholar 

  47. Li J, Zheng W, Kwon AH, et al. In vitro selection and characterization of a highly efficient Zn(II)-dependent RNA-cleaving deoxyribozyme. Nucleic Acids Res 2000; 28: 481–8

    Article  PubMed  CAS  Google Scholar 

  48. Feldman AR, Sen D. A new and efficient DNA enzyme for the sequence-specific cleavage of RNA. J Mol Biol 2001; 313: 283–94

    Article  PubMed  CAS  Google Scholar 

  49. Michienzi A, Rossi JJ. Intracellular applications of ribozymes. Methods Enzymol 2001; 341: 581–96

    Article  PubMed  CAS  Google Scholar 

  50. Uhlmann E, Peyman A. Antisense oligonucleotides: a new therapeutic principle. Chem Rev 1990; 90: 543–84

    Article  CAS  Google Scholar 

  51. Usman N, Blatt LM. Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics. J Clin Invest 2000; 106: 1197–202

    Article  PubMed  CAS  Google Scholar 

  52. Beigelman L, McSwiggen JA, Draper KG, et al. Chemical modification of hammerhead ribozymes: catalytic activity and nuclease resistance. J Biol Chem 1995; 270: 25702–8

    Article  PubMed  CAS  Google Scholar 

  53. Sioud M, Leirdal M. Design of nuclease resistant protein kinase Cot DNA enzymes with potential therapeutic application. J Mol Biol 2000; 296: 937–47

    Article  PubMed  CAS  Google Scholar 

  54. Amarzguioui M, Brede G, Babaie E, et al. Secondary structure prediction and in vitro accessibility of mRNA as tools in the selection of target sites for ribozymes. Nucleic Acids Res 2000; 28: 4113–24

    Article  PubMed  CAS  Google Scholar 

  55. Scherr M, Rossi JJ, Sczakiel G, et al. RNA accessibility prediction: a theoretical approach is consistent with experimental studies in cell extracts. Nucleic Acids Res 2000; 28: 2455–61

    Article  PubMed  CAS  Google Scholar 

  56. Birikh KR, Berlin YA, Soreq H, et al. Probing accessible sites for ribozymes on human acetylcholinesterase RNA. RNA 1997; 3: 429–37

    PubMed  CAS  Google Scholar 

  57. Scherr M, Rossi JJ. Rapid determination and quantitation of the accessibility to native RNAs by antisense oligodeoxynucleotides in murine cell extracts. Nucleic Acids Res 1998; 26: 5079–85

    Article  PubMed  CAS  Google Scholar 

  58. Scherr M, Reed M, Huang CF, et al. Oligonucleotide scanning of native mRNAs in extracts predicts intracellular ribozyme efficiency: ribozyme-mediated reduction of the murine DNA methyltransferase. Mol Ther 2000; 2: 26–38

    Article  PubMed  CAS  Google Scholar 

  59. Pan WH, Devlin HF, Kelley C, et al. A selection system for identifying accessible sites in target RNAs. RNA 2001; 7: 610–21

    Article  PubMed  CAS  Google Scholar 

  60. Lieber A, Strauss M. Selection of efficient cleavage sites in target RNAs by using a ribozyme expression library. Mol Cell Biol 1995; 15: 540–51

    PubMed  CAS  Google Scholar 

  61. Sriram B, Banerjea AC. In vitro-selected RNA cleaving DNA enzymes from a combinatorial library are potent inhibitors of HIV-1 gene expression. Biochem J 2000; 352: 667–73

    Article  PubMed  CAS  Google Scholar 

  62. Warashina M, Kuwabara T, Kata Y, et al. RNA-protein hybrid ribozymes that efficiently cleave any mRNA independently of the structure of the target RNA. Proc Natl Acad Sci U S A 2001; 98: 5572–7

    Article  PubMed  CAS  Google Scholar 

  63. Kawasaki H, Taira K. Identification of genes by hybrid ribozymes that couple cleavage activity with the unwinding activity of an endogenous RNA helicase. EMBO Rep 2002; 3: 443–50

    Article  PubMed  CAS  Google Scholar 

  64. Denman RB, Smedman M, Ju W, et al. Ribozyme mediated degradation of beta-amyloid peptide precursor mRNA in COS-7 cells. Nucleic Acids Res 1994; 22: 2375–82

    Article  PubMed  CAS  Google Scholar 

  65. Denman RB, Smedman M, Abraham M, et al. Facilitated reduction of beta-amyloid peptide precursor by synthetic oligonucleotides in COS-7 cells expressing a hammerhead ribozyme. Arch Biochem Biophys 1997; 348: 82–90

    Article  PubMed  CAS  Google Scholar 

  66. Flory CM, Pavco PA, Jarvis TC, et al. Nuclease-resistant ribozymes decrease stromelysin mRNA levels in rabbit synovium following exogenous delivery to the knee joint. Proc Natl Acad Sci U S A 1996; 93: 754–8

    Article  PubMed  CAS  Google Scholar 

  67. Irminger-Finger I, Soriano JV, Vaudan G, et al. In vitro repression of Brcal-as-sociated RING domain gene, Bard1, induces phenotypic changes in mammary epithelial cells. J Cell Biol 1998; 143: 1329–39

    Article  PubMed  CAS  Google Scholar 

  68. Tokunaga T, Tsuchida T, Kijima H, et al. Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line. Br J Cancer 2000; 83: 833–9

    Article  PubMed  CAS  Google Scholar 

  69. Soeth E, Wirth T, List HJ, et al. Controlled ribozyme targeting demonstrates an antiapoptotic effect of carcinoembryonic antigen in HT29 colon cancer cells. Clin Cancer Res 2001; 7: 2022–30

    PubMed  CAS  Google Scholar 

  70. Yokoyama Y, Wan X, Shinohara A, et al. Hammerhead ribozymes to modulate telomerase activity of endometrial carcinoma cells. Hum Cell 2001; 14: 223–31

    PubMed  CAS  Google Scholar 

  71. Scanlon KJ, Jiao L, Funato T, et al. Ribozyme-mediated cleavage of c-fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein. Proc Natl Acad Sci U S A 1991; 88: 10591–5

    Article  PubMed  CAS  Google Scholar 

  72. Sioud M, Natvig JB, Forre O. Preformed ribozyme destroys tumour necrosis factor mRNA in human cells. J Mol Biol 1992; 223: 831–5

    Article  PubMed  CAS  Google Scholar 

  73. Czubayko F, Riegel AT, Wellstein A. Ribozyme-targeting elucidates a direct role of pleiotrophin in tumor growth. J Biol Chem 1994; 269: 21358–63

    PubMed  CAS  Google Scholar 

  74. Kobayashi H, Dorai T, Holland JF, et al. Reversal of drug sensitivity in multidrug-resistant tumor cells by an MDR1 (PGY1) ribozyme. Cancer Res 1994; 54: 1271–5

    PubMed  CAS  Google Scholar 

  75. Feng M, Cabrera G, Deshane J, et al. Neoplastic reversion accomplished by high efficiency adenoviral-mediated delivery of an anti-ras ribozyme. Cancer Res 1995; 55: 2024–8

    PubMed  CAS  Google Scholar 

  76. Czubayko F, Downing SG, Hsieh SS, et al. Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation. Gene Ther 1997; 4: 943–9

    Article  PubMed  CAS  Google Scholar 

  77. Ma M, Benimetskaya L, Lebedeva I, et al. Intracellular mRNA cleavage induced through activation of RNase P by nuclease-resistant external guide sequences. Nat Biotechnol 2000; 18: 58–61

    Article  PubMed  CAS  Google Scholar 

  78. Parry TJ, Cushman C, Gallegos AM, et al. Bioactivity of anti-angiogenic ribozymes targeting Flt-1 and KDR mRNA. Nucleic Acids Res 1999; 27: 2569–77

    Article  PubMed  CAS  Google Scholar 

  79. Pavco PA, Bouhana KS, Gallegos AM, et al. Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. Clin Cancer Res 2000; 6: 2094–103

    PubMed  CAS  Google Scholar 

  80. Hatanaka H, Abe Y, Naruke M, et al. Modulation of multidrug resistance in a cancer cell line by anti-multidrug resistance-associated protein (MRP) ribozyme. Anticancer Res 2001; 21: 879–85

    PubMed  CAS  Google Scholar 

  81. Liu C, Cheng R, Sun LQ, et al. Suppression of platelet-type 12-lypoxygenase activity in human erythroleukemia cells by an RNA-cleaving DNAzyme. Biochem Biophys Res Commun 2001; 284: 1077–82

    Article  PubMed  CAS  Google Scholar 

  82. Weng DE, Usman N. Angiozyme: a novel angiogenesis inhibitor. Curr Oncol Rep 2001; 3: 141–6

    Article  PubMed  CAS  Google Scholar 

  83. Cieslak M, Niewiarowska J, Nawrot M, et al. DNAzymes to β1 and β3 mRNA down-regulate expression of the targeted integrins and inhibit endothelial cell capillary tube formation in fibrin and matrigel. J Biol Chem 2002; 277: 6779–87

    Article  PubMed  CAS  Google Scholar 

  84. Leirdal M, Sioud M. Ribozyme inhibition of the protein kinase C alpha triggers apoptosis in glioma cells. Br J Cancer 1999; 80: 1558–64

    Article  PubMed  CAS  Google Scholar 

  85. Kanazawa Y, Ohkawa K, Ueda K, et al. Hammerhead ribozyme-mediated inhibition of telomerase activity in extracts of human hepatocellular carcinoma cells. Biochem Biophys Res Commun 1996; 225: 570–6

    Article  PubMed  CAS  Google Scholar 

  86. Oshika Y, Nakamura M, Tokunaga T, et al. Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC). Eur J Cancer 2000; 36: 2390–6

    Article  PubMed  CAS  Google Scholar 

  87. Kashani-Sabet M, Funato T, Florenes VA, et al. Suppression of the neoplastic phenotype in vivo by an anti-ras ribozyme. Cancer Res 1994; 54: 900–2

    PubMed  CAS  Google Scholar 

  88. Czubayko F, Schulte AM, Berchem GJ, et al. Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin. Proc Natl Acad Sci U S A 1996; 93: 14753–8

    Article  PubMed  CAS  Google Scholar 

  89. Maelandsmo GM, Hovig E, Skrede M, et al. Reversal of the in vivo metastatic phenotype of human tumor cells by an anti-CAPL (mtsl) ribozyme. Cancer Res 1996; 56: 5490–8

    PubMed  CAS  Google Scholar 

  90. Yokoyama Y, Morishita S, Takahashi Y, et al. Modulation of c-fms proto-oncogene in an ovarian carcinoma cell line by a hammerhead ribozyme. Br J Cancer 1997; 76: 977–82

    Article  PubMed  CAS  Google Scholar 

  91. Chen S, Song CS, Lavrovsky Y, et al. Catalytic cleavage of the androgen receptor messenger RNA and functional inhibition of androgen receptor activity by a hammerhead ribozyme. Mol Endocrinol 1998; 12: 1558–66

    Article  PubMed  CAS  Google Scholar 

  92. Dorai T, Perlman H, Walsh K, et al. A recombinant defective adenoviral agent expressing anti-bcl-2 ribozyme promotes apoptosis of bcl-2-expressing human prostate cancer cells. Int J Cancer 1999; 82: 846–52

    Article  PubMed  CAS  Google Scholar 

  93. Xu ZD, Oey L, Mohan S, et al. Hammerhead ribozyme-mediated cleavage of the human insulin-like growth factor-II ribonucleic acid in vitro and in prostate cancer cells. Endocrinology 1999; 140: 2134–44

    Article  PubMed  CAS  Google Scholar 

  94. Benedict CM, Pan W, Loy SE, et al. Triple ribozyme-mediated down-regulation of the retinoblastoma gene. Carcinogenesis 1998; 19: 1223–30

    Article  PubMed  CAS  Google Scholar 

  95. De Young MB, Kincade-Denker J, Boehm CA, et al. Functional characterization of ribozymes expressed using U1 and T7 vectors for the intracellular cleavage of ANF mRNA. Biochemistry 1994; 33: 12127–38

    Article  PubMed  Google Scholar 

  96. Macejak DG, Lin H, Webb S, et al. Adenovirus-mediated expression of a ribozyme to c-myb mRNA inhibits smooth muscle cell proliferation and neointima formation in vivo. J Virol 1999; 73: 7745–51

    PubMed  CAS  Google Scholar 

  97. Frimerman A, Welch PJ, Jin X, et al. Chimeric DNA-RNA hammerhead ribozyme to proliferating cell nuclear antigen reduces stent-induced stenosis in a porcine coronary model. Circulation 1999; 99: 697–703

    Article  PubMed  CAS  Google Scholar 

  98. Sun LQ, Cairns MJ, Gerlach WL, et al. Suppression of smooth muscle cell proliferation by a c-myc RNA-cleaving deoxyribozyme. J Biol Chem 1999; 274: 17236–41

    Article  PubMed  CAS  Google Scholar 

  99. Perlman H, Sata M, Krasinski K, et al. Adenovirus-encoded hammerhead ribozyme to Bcl-2 inhibits neointimal hyperplasia and induces vascular smooth muscle cell apoptosis. Cardiovasc Res 2000; 45: 570–8

    Article  PubMed  CAS  Google Scholar 

  100. Gu JL, Pei H, Thomas L, et al. Ribozyme-mediated inhibition of rat leukocyte-type 12-lipoxygenase prevents intimai hyperplasia in balloon-injured rat carotid arteries. Circulation 2001; 103: 1446–52

    Article  PubMed  CAS  Google Scholar 

  101. Khachigian LM, Fahmy RG, Zhang G, et al. c-Jun regulates vascular smooth muscle cell growth and neointima formation after arterial injury. J Biol Chem 2002; 277: 22985–91

    Article  PubMed  CAS  Google Scholar 

  102. Lowe HC, Chesterman CN, Khachigian LM. Catalytic antisense DNA molecules targeting erg-1 inhibit neointima formation following permanent ligation of rat common carotid arteries. Thromb Haemost 2002; 87: 134–40

    PubMed  CAS  Google Scholar 

  103. Efrat S, Leiser M, Wu YJ, et al. Ribozyme-mediated attenuation of pancreatic beta-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion. Proc Natl Acad Sci U S A 1994; 91: 2051–5

    Article  PubMed  CAS  Google Scholar 

  104. Goila R, Banerjea AC. Inhibition of hepatitis B virus X gene expression by novel DNA enzymes. Biochem J 2001; 353: 701–8

    Article  PubMed  CAS  Google Scholar 

  105. Lee PA, Blatt LM, Blanchard KS, et al. Pharmacokinetics and tissue distribution of a ribozyme directed against hepatitis C virus RNA following subcutaneous or intravenous administration in mice. Hepatology 2000; 32: 640–6

    Article  PubMed  CAS  Google Scholar 

  106. Macejak DG, Jensen KL, Jamison SF, et al. Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes. Hepatology 2000; 31: 769–76

    Article  PubMed  CAS  Google Scholar 

  107. Chen CJ, Banerjea AC, Harmison GG, et al. Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication: potential effectiveness against most presently sequenced HIV-1 isolates. Nucleic Acids Res 1992; 20: 4581–9

    Article  PubMed  CAS  Google Scholar 

  108. Ojwang JO, Hampel A, Looney DJ, et al. Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci U S A 1992; 89: 10802–6

    Article  PubMed  CAS  Google Scholar 

  109. Yu M, Ojwang J, Yamada O, et al. A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 1993; 90: 6340–4

    Article  PubMed  CAS  Google Scholar 

  110. Zhou C, Bahner IC, Larson GP, et al. Inhibition of HIV-1 in human T-lymphocytes by retrovirally transduced anti-tat and rev hammerhead ribozymes. Gene 1994; 149: 33–9

    Article  PubMed  CAS  Google Scholar 

  111. Sun LQ, Pyati J, Smythe J, et al. 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 U S A 1995; 92: 7272–6

    Article  PubMed  CAS  Google Scholar 

  112. Sun LQ, Wang L, Gerlach WL, et al. Target sequence-specific inhibition of HIV-1 replication by ribozymes directed to tat RNA. Nucleic Acids Res 1995; 23: 2909–13

    Article  PubMed  CAS  Google Scholar 

  113. Michienzi A, Prislei S, Bozzoni I. U1 small nuclear RNA chimeric ribozymes with substrate specificity for the Rev pre-mRNA of human immunodeficiency virus. Proc Natl Acad Sci U S A 1996; 93: 7219–24

    Article  PubMed  CAS  Google Scholar 

  114. Heusch M, Kraus G, Johnson P, et al. Intracellular immunization against SIVmac utilizing a hairpin ribozyme. Virology 1996; 216: 241–4

    Article  PubMed  CAS  Google Scholar 

  115. Larsson S, Hotchkiss G, Su J, et al. A novel ribozyme target site located in the HIV-1 nef open reading frame. Virology 1996; 219: 161–9

    Article  PubMed  CAS  Google Scholar 

  116. Zhou C, Bahner I, Rossi JJ, et al. Expression of hammerhead ribozymes by retroviral vectors to inhibit HIV-1 replication: comparison of RNA levels and viral inhibition. Antisense Nucleic Acid Drug Dev 1996; 6: 17–24

    Article  PubMed  Google Scholar 

  117. Bauer G, Valdez P, Kearns K, et al. Inhibition of human immunodeficiency virus-1 (HIV-1) replication after transduction of granulocyte colony-stimulating factor-mobilized CD34+ cells from HIV-1-infected donors using retroviral vectors containing anti-HIV-1 genes. Blood 1997; 89: 2259–67

    PubMed  CAS  Google Scholar 

  118. Wang L, Witherington C, King A, et al. Preclinical characterization of an anti-tat ribozyme for therapeutic application. Hum Gene Ther 1998; 9: 1283–91

    Article  PubMed  CAS  Google Scholar 

  119. Dash BC, Harikrishnan TA, Goila R, et al. Targeted cleavage of HIV-1 envelope gene by a DNA enzyme and inhibition of HIV-1 envelope-CD4 mediated cell fusion. FEBS Lett 1998; 431: 395–9

    Article  PubMed  CAS  Google Scholar 

  120. Wong-Staal F, Poeschla EM, Looney DJ. A controlled, phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA. Hum Gene Ther 1998; 9: 2407–25

    Article  PubMed  CAS  Google Scholar 

  121. Amado RG, Mitsuyasu RT, Symonds G, et al. A phase I trial of autologous CD34+ hematopoietic progenitor cells transduced with an anti-HIV ribozyme. Hum Gene Ther 1999; 10: 2255–70

    Article  PubMed  CAS  Google Scholar 

  122. Zhang X, Xu Y, Ling H, et al. Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme. FEBS Lett 1999; 458: 151–6

    Article  PubMed  CAS  Google Scholar 

  123. Bai J, Rossi J, Akkina R. Multivalent anti-CCR ribozymes for stem cell-based HIV type 1 gene therapy. AIDS Res Hum Retroviruses 2001; 17: 385–99

    Article  PubMed  CAS  Google Scholar 

  124. Kraus G, Geffin R, Spruill G, et al. Cross-clade inhibition of HIV-1 replication and cytopathology by using RNase P-associated external guide sequences. Proc Natl Acad Sci U S A 2002; 99: 3406–11

    Article  PubMed  CAS  Google Scholar 

  125. Yen L, Strittmatter SM, Kalb RG. Sequence-specific cleavage of Huntington mRNA by catalytic DNA. Ann Neurol 1999; 46: 366–73

    Article  PubMed  CAS  Google Scholar 

  126. Mahieu M, Deschuyteneer R, Forget D, et al. Construction of a ribozyme directed against human interleukin-6 mRNA: evaluation of its catalytic activity in vitro and in vivo. Blood 1994; 84: 3758–65

    PubMed  CAS  Google Scholar 

  127. Tang XB, Hobom G, Luo D. Ribozyme mediated destruction of influenza A virus in vitro and in vivo. J Med Virol 1994; 42: 385–95

    Article  PubMed  CAS  Google Scholar 

  128. Plehn-Dujowich D, Altman S. Effective inhibition of influenza virus production in cultured cells by external guide sequences and ribonuclease P. Proc Natl Acad Sci U S A 1998; 95: 7327–32

    Article  PubMed  CAS  Google Scholar 

  129. Toyoda T, Imamura Y, Takaku H, et al. Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme. FEBS Lett 2000; 481: 113–6

    Article  PubMed  CAS  Google Scholar 

  130. Kozu T, Sueoka E, Okabe S, et al. Designing of chimeric DNA/RNA hammerhead ribozymes to be targeted against AML1/MTG8 mRNA. J Cancer Res Clin Oncol 1996; 122: 254–6

    Article  PubMed  CAS  Google Scholar 

  131. Szyrach M, Munchberg FE, Riehle H, et al. Cleavage of AML1/MTG8 by asymmetric hammerhead ribozymes. Eur J Biochem 2001; 268: 3550–7

    Article  PubMed  CAS  Google Scholar 

  132. Shore SK, Nabissa PM, Reddy EP. Ribozyme-mediated cleavage of the BCRABL oncogene transcript: in vitro cleavage of RNA and in vivo loss of P210 protein-kinase activity. Oncogene 1993; 8: 3183–8

    PubMed  CAS  Google Scholar 

  133. Snyder DS, Wu Y, Wang JL, et al. Ribozyme-mediated inhibition of bcr-abl gene expression in a Philadelphia chromosome-positive cell line. Blood 1993; 82: 600–5

    PubMed  CAS  Google Scholar 

  134. Kuwabara T, Warashina M, Tanabe T, et al. A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo. Mol Cell 1998; 2: 617–27

    Article  PubMed  CAS  Google Scholar 

  135. Wu Y, Yu L, McMahon R, et al. Inhibition of bcr-abl oncogene expression by novel deoxyribozymes (DNAzymes). Hum Gene Ther 1999; 10: 2847–57

    Article  PubMed  CAS  Google Scholar 

  136. Cobaleda C, Sanchez-Garcia I. In vivo inhibition by a site-specific catalytic RNA subunit of RNase P designed against the BCR-ABL oncogenic products: a novel approach for cancer treatment. Blood 2000; 95: 731–7

    PubMed  CAS  Google Scholar 

  137. Hubinger G, Schmid M, Linortner S, et al. Ribozyme-mediated cleavage of wt1 transcripts suppresses growth of leukemia cells. Exp Hematol 2001; 29: 1226–35

    Article  PubMed  CAS  Google Scholar 

  138. Iversen PO, Sioud M. Modulation of granulocyte-macrophage colony-stimulating factor gene expression by a tumor necrosis factor specific ribozyme in juvenile myelomonocytic leukemic cells. Blood 1998; 92: 4263–8

    PubMed  CAS  Google Scholar 

  139. Suwanai H, Matsushita H, Kobayashi H, et al. A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: improved design of maxizymes against PML/RARα mRNA. Int J Oncol 2002; 20: 127–30

    PubMed  CAS  Google Scholar 

  140. Lewin AS, Drenser KA, Hauswirth WW, et al. Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat Med 1998; 4: 967–71

    Article  PubMed  CAS  Google Scholar 

  141. Lieber A, He CY, Polyak SJ, et al. Elimination of hepatitic C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes. J Virol 1996; 70: 8782–91

    PubMed  CAS  Google Scholar 

  142. Sakamoto N, Wu CH, Wu GY. Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by hammerhead ribozymes. J Clin Invest 1996; 98: 2720–8

    Article  PubMed  CAS  Google Scholar 

  143. Welch PJ, Tritz R, Yei S, et al. A potential therapeutic application of hairpin ribozymes: in vitro and in vivo studies of gene therapy for hepatitis C virus infection. Gene Ther 1996; 3: 994–1001

    PubMed  CAS  Google Scholar 

  144. Macejak DG, Jensen KL, Pavco PA, et al. Enhanced antiviral effect in cell culture of type I interferon and ribozymes targeting HCV RNA. J Viral Hepat 2001; 8: 400–5

    Article  PubMed  CAS  Google Scholar 

  145. Sandberg JA, Rossi S, Gordon GS, et al. Safety analysis of a phase I study of HEPTAZYME™, a nuclease resistant ribozyme targeting hepatitis C (HCV) RNA. Boulder (CO): Ribozyme Pharmaceuticals Inc., 2001 (Data on file)

    Google Scholar 

  146. Sandberg JA, Parker VP, Blanchard KS, et al. Pharmacokinetics and tolerability of an antiangiogenic ribozyme (ANGIOZYME™) targeting vascular endothelial growth factor receptor mRNA in the cynomolgus monkey. Antisense Nucleic Acid Drug Dev 2000; 10: 153–62

    Article  PubMed  CAS  Google Scholar 

  147. Weng DE, Weiss P, Kellacky C, et al. A phase I/II study of repetitive dose Angiozyme™, a ribozyme targeting the flt-1 receptor for VEGF. Proceedings of the 11 th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy; 2000 Nov 7, Amsterdam

  148. Cobaleda C, Sanchez-Garcia I. RNase P: from biological function to biotechno-logical application. Trends Biotechnol 2001; 19: 406–11

    Article  PubMed  CAS  Google Scholar 

  149. Dunn W, Trang P, Khan U, et al. RNase P-mediated inhibition of cytomegalovirus protease expression and viral DNA encapsidation by oligonucleotide external guide sequences. Proc Natl Acad Sci U S A 2001; 98: 14831–6

    Article  PubMed  CAS  Google Scholar 

  150. Watanabe T, Sullenger BA. RNA repair: a novel approach to gene therapy. Adv Drug Deliv Rev 2000; 44: 109–18

    Article  PubMed  CAS  Google Scholar 

  151. Sullenger BA, Cech TR. Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature 1994; 371: 619–22

    Article  PubMed  CAS  Google Scholar 

  152. Kohler U, Ayre BG, Goodman HM, et al. Trans-spicing ribozymes for targeted gene delivery. J Mol Biol 1999; 285: 1935–50

    Article  PubMed  CAS  Google Scholar 

  153. Zarrinkar PP, Sullenger BA. Optimizing the substrate specificity of a group I intron ribozyme. Biochemistry 1999; 38: 3426–32

    Article  PubMed  CAS  Google Scholar 

  154. Lan N, Howrey RP, Lee SW, et al. Ribozyme-mediated repair of sickle β-globin mRNA in erythrocyte precursor. Science 1998; 280: 1593–6

    Article  PubMed  CAS  Google Scholar 

  155. Phylactou LA, Darrah C, Wood MJ. Ribozyme-mediated trans-splicing of a trinucleotide repeat. Nat Genet 1998; 18: 378–81

    Article  PubMed  CAS  Google Scholar 

  156. Watanabe T, Sullenger BA. Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts. Proc Natl Acad Sci U S A 2000; 97: 8490–4

    Article  PubMed  CAS  Google Scholar 

  157. Eskes R, Yang J, Lambowitz AM, et al. Mobility of yeast mitochondrial group II introns: engineering a new site specificity and retrohoming via full reverse splicing. Cell 1997; 88: 865–74

    Article  PubMed  CAS  Google Scholar 

  158. Cousineau B, Smith D, Lawrence-Cavanagh S, et al. Retrohoming of a bacterial group II intron: mobility via complete reverse splicing, independent of homologous DNA recombination. Cell 1998; 94: 451–62

    Article  PubMed  CAS  Google Scholar 

  159. Guo H, Karberg M, Long M, et al. Group II introns designed to insert into therapeutically relevant DNA target sites in human cells. Science 2000; 289: 452–7

    Article  PubMed  CAS  Google Scholar 

  160. Kawasaki H, Onuki R, Suyama E, et al. Identification of genes that function in the TNF-α-mediated apoptotic pathway using randomized hybrid ribozyme libraries. Nat Biotechnol 2002; 20: 376–80

    Article  PubMed  CAS  Google Scholar 

  161. Soukup GA, Breaker RR. Nucleic acid molecular switches. Trends Biotechnol 1999; 17: 469–76

    Article  PubMed  CAS  Google Scholar 

  162. Breaker RR. Engineered allosteric ribozymes as biosensor components. Curr Opin Biotechnol 2002; 13: 31–9

    Article  PubMed  CAS  Google Scholar 

  163. Tang J, Breaker RR. Rational design of allosteric ribozymes. Chem Biol 1997; 4: 453–9

    Article  PubMed  CAS  Google Scholar 

  164. Soukup GA, Breaker RR. Engineering precision RNA molecular switches. Proc Natl Acad Sci U S A 1999; 96: 3584–9

    Article  PubMed  CAS  Google Scholar 

  165. Koizumi M, Soukup GA, Kerr JN, et al. Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP. Nat Struct Biol 1999; 6: 1062–71

    Article  PubMed  CAS  Google Scholar 

  166. Piganeau N, Jenne A, Thuillier V, et al. An allosteric ribozyme regulated by doxycycline. Angew Chem Int Ed Engl 2000; 39: 4369–73

    Article  CAS  Google Scholar 

  167. Robertson MP, Ellington AD. In vitro selection of nucleoprotein enzymes. Nat Biotechnol 2001; 19: 650–5

    Article  PubMed  CAS  Google Scholar 

  168. Soukup GA, DeRose EC, Koizumi M, et al. Generating new ligand-binding RNAs by affinity maturation and disintegration of allosteric ribozymes. RNA 2001; 7: 524–36

    Article  PubMed  CAS  Google Scholar 

  169. Robertson MP, Ellington AD. In vitro selection of an allosteric ribozyme that transduces analytes to amplicons. Nat Biotechnol 1999; 17: 62–6

    Article  PubMed  CAS  Google Scholar 

  170. Soukup GA, Emilsson GAM, Breaker RR. Altering molecular recognition of RNA aptamers by allosteric selection. J Mol Biol 2000; 298: 623–32

    Article  PubMed  CAS  Google Scholar 

  171. Robertson MP, Ellington AD. Design and optimization of effector-activated ribozyme ligases. Nucleic Acids Res 2000; 28: 1751–9

    Article  PubMed  CAS  Google Scholar 

  172. Kertsburg A, Soukup GA. A versatile communication module for controlling RNA folding and catalysis. Nucleic Acids Res 2002; 30: 4599–606

    Article  PubMed  CAS  Google Scholar 

  173. Levy M, Ellington AD. ATP-dependent allosteric DNA enzymes. Chem Biol 2002: 9: 417–26

    Article  PubMed  CAS  Google Scholar 

  174. Wang DY, Lai BH, Sen D. A general strategy for effector-mediated control of RNA-cleaving ribozymes and DNA enzymes. J Mol Biol 2002; 318: 33–43

    Article  PubMed  CAS  Google Scholar 

  175. Hartig JS, Najifi-Shoushtari SH, Grune I, et al. Protein-dependent ribozymes report molecular interactions in real time. Nat Biotechnol 2002; 20: 717–22

    Article  PubMed  CAS  Google Scholar 

  176. Vaish NK, Dong F, Andrews L, et al. Monitoring post-translational modification of proteins with allosteric ribozymes. Nat Biotechnol 2002; 20: 810–5

    PubMed  CAS  Google Scholar 

  177. Wang DY, Sen D. Rationally designed allosteric variants of hammerhead ribozymes responsive to the HIV-1 Tat protein. Comb Chem High Throughput Screen 2002; 5: 301–12

    Article  PubMed  CAS  Google Scholar 

  178. Kuwabara T, Warashina M, Tanabe T, et al. A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo. Mol Cell 1998; 2: 617–27

    Article  PubMed  CAS  Google Scholar 

  179. Tanabe T, Takata I, Kuwabara T, et al. Maxizymes, novel allosterically controllable ribozymes, can be designed to cleave various substrates. Biomacromolecules 2002; 1: 108–17

    Article  CAS  Google Scholar 

  180. Wang DY, Sen D. A novel mode of regulation of an RNA-cleaving DNAzyme by effectors that bind to both enzyme and substrate. J Mol Biol 2001; 310: 723–34

    Article  PubMed  CAS  Google Scholar 

  181. Burke DH, Ozerova ND, Nilsen-Hamilton M. Allosteric hammerhead ribozyme TRAPs. Biochemistry 2002; 41: 6588–94

    Article  PubMed  CAS  Google Scholar 

  182. Wang DY, Lai BH, Feldman AR, et al. A general approach for the use of oligonucleotide effectors to regulate the catalysis of RNA-cleaving ribozymes and DNAzymes. Nucleic Acids Res 2002; 30: 1735–42

    Article  PubMed  CAS  Google Scholar 

  183. Stojanovic MN, de Prada P, Landry DW. Homogeneous assays based on deoxyribozyme catalysis. Nucleic Acids Res 2000; 28: 2915–8

    Article  PubMed  CAS  Google Scholar 

  184. Frauendorf C, Jaschke A. Detection of small organic analytes by fluorescing molecular switches. Bioorg Med Chem 2001; 9: 2521–4

    Article  PubMed  CAS  Google Scholar 

  185. Seetharaman S, Zivarts M, Sudarsan N, et al. Immobilized RNA switches for the analysis of complex chemical and biological mixtures. Nat Biotechnol 2001; 19: 336–41

    Article  PubMed  CAS  Google Scholar 

  186. Tanabe T, Kuwabara T, Warashina M, et al. Oncogene inactivation in a mouse model. Nature 2000; 406: 473–4

    Article  PubMed  CAS  Google Scholar 

  187. Kuwabara T, Tanabe T, Warashina M, et al. Allosterically controllable maxizyme-mediated suppression of progression of leukemia in mice. Biomacromolecules 2001; 2: 1220–8

    Article  PubMed  CAS  Google Scholar 

  188. Cairns MJ, King A, Sun LQ. Nucleic acid mutation analysis using catalytic DNA. Nucleic Acids Res 2000; 28: E9

    Article  PubMed  CAS  Google Scholar 

  189. Todd AV, Fuery CJ, Impey HL, et al. DzyNA-PCR: use of DNAzymes to detect and quantify nucleic acid sequences in a real-time fluorescent format. Clin Chem 2000; 46: 625–30

    PubMed  CAS  Google Scholar 

  190. Hannon GJ. RNA interference. Nature 2002; 418: 244–51

    Article  PubMed  CAS  Google Scholar 

  191. Tuschl T. Expanding small RNA interference. Nat Biotechnol 2002; 20: 446–8

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Dr Soukup is supported by grants from the Nebraska NSF EPSCoR and the Health Future Foundation. The authors have no conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska, 68178, USA

    David Steele, Alexis Kertsburg &  Garrett A. Soukup

Authors
  1. David Steele
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexis Kertsburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Garrett A. Soukup
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Garrett A. Soukup.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steele, D., Kertsburg, A. & Soukup, G.A. Engineered Catalytic RNA and DNA. Am J Pharmacogenomics 3, 131–144 (2003). https://doi.org/10.2165/00129785-200303020-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129785-200303020-00006

Keywords

Search

Navigation