Antisense and Ribozymes


Antisense–ribozyme technology has evolved from being a tool in molecular biology to being used as a therapeutic agent in human disease. There is enormous potential in antisense and ribozyme therapy, but significant pitfalls and obstacles have yet to be overcome.

Keywords: phosphorothioate oligodeoxynucleotides; cationic liposomes; retroviral vector; adenoviral vector; multidrug resistance; biological therapy

Figure 1.

Conserved sequences of the hammerhead ribozyme and position relative to its target ribonucleic acid (RNA). The conventional numbering system for the specific bases has been included. Required bases have been identified; other variable bases have been designated as ‘N’. Cleavage occurs 3′ to the N at position 17.

Figure 2.

Consensus sequences of the hairpin ribozyme and position relative to its substrate.



Benimetskaya L, Loike JD, Khaled Z, et al. (1997) Mac‐1 (CD11b–CD18) is an oligodeoxynucleotide‐binding protein. Nature Medicine 3: 414–420.

Dean NM and McKay R (1994) Inhibition of protein kinase C‐alpha expression in mice after systemic administration of phosphorothioate antisense oligodeoxynucleotides. Proceedings of the National Academy of Sciences of the United States of America 91: 11762–11766.

Guerrier‐Takada C, Cardiner K, March T, et al. (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35: 849–857.

Jansen B, Schlagbauer‐Wadl H, Brown BD, et al. (1998) bcl‐2 antisense therapy chemosensitizes human melanoma in SCID mice. Nature Medicine 4: 232–234.

Kashani‐Sabet M, Yong L, Fong S, et al. (2002) Identification of gene function and functional pathways by systemic plasmid‐based ribozyme targeting in adult mice. Proceedings of the National Academy of Sciences of the United States of America 99: 3878–3883.

Monia BP, Johnston JF, Geiger T, et al. (1996) Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against c‐raf kinase. Nature Medicine 2: 668–675.

Ojwang JO, Hampel A, Looney DJ, et al. (1992) Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proceedings of the National Academy of Sciences of the United States of America 89: 10802–10806.

Sarver N, Cantin EM, Chang PS, et al. (1990) Ribozymes as potential anti‐HIV‐1 therapeutic agents. Science 247: 1222–1225.

Scanlon KJ, Jiao L, Funato T, et al. (1991) Ribozyme‐mediated cleavage of c‐fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein. Proceedings of the National Academy of Sciences of the United States of America 88: 10591–10595.

Zamecnik PC and Stephenson ML (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proceedings of the National Academy of Sciences of the United States of America 75: 280–284.

Zaug AJ and Cech TR (1986) The intervening sequence RNA of Tetrahymena is an enzyme. Science 231: 470–475.

Further Reading

Haseloff J and Gerlach WL (1988) Simple RNA enzymes with new and highly specific endoribonuclease activity. Nature 334: 585–591.

Irie A, Kijima H, Ohkawa T, et al. (1997) Anti‐oncogene ribozymes for cancer gene therapy. Advances in Pharmacology 40: 207–257.

Krieg AM, Yi AK, Matson S, et al. (1995) CpG motifs in bacterial DNA trigger direct B‐cell activation. Nature 374: 546–549.

Lebedeva I and Stein CA (2001) Antisense oligonucleotides: promise and reality. Annual Review of Pharmacology and Toxicology 41: 403–419.

Stein CA (2001) The experimental use of antisense oligonucleotides: a guide for the perplexed. Journal of Clinical Investigation 108: 641–644.

Szczylik C, Skorski T, Nicolaides NC, et al. (1991) Selective inhibition of leukemia cell proliferation by BCR‐ABL antisense oligonucleotides. Science 253: 562–565.

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Scanlon, Kevin, and Kashani‐Sabet, Mohammed(Jan 2006) Antisense and Ribozymes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005762]