Antisense drug

Strategies such as antisense nucleotides, which would inactivate the specific mRNA encoded by cytokine genes or cytokine receptor genes, may be a more fhiitfiil approach in the future when the problems of stability, cell penetration and delivery have been resolved (Colman, 1990). 

Wide range including malignant lymphomas, malanomas and sarcomas. 

Active against cancers of the brain and cerebrospinal fluid. 

SELECTED EXAMPLES OF DRUG ACTION AT SOME COMMON TARGET AREAS 

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Peptoids have also shown great utility in their ability to complex with and deliver nucleic acids to cells, a critical step toward the development of antisense drugs, DNA vaccines, or gene-based therapeutics. Most non-viral nucleic acid delivery systems are based on cationic molecules that can form complexes with the polyan-... 

Lebedeva I., Stein C.A., Annu. Rev. Pharmacol. Toxicol. 2001, 43, 403-419. Antisense Drug Technology - Principles, Strategies and Applications, Crooke S.T. (Ed.). M. Decker, 2001. 

Oligonucleotide-based drugs such as antisense drugs, aptamers, and small interfering RNA (siRNA) have attracted considerable attention as promising therapeutic agents for the treatment of various human diseases [59], To develop... 

Phillips, M. 2000. Antisense Technology. Methods in Enzymology, volume 313. Academic Press. Crooke, S. (Ed.) 2001. Antisense Drug Technology. Marcel Dekker. 

Antisense Approach This is a relatively new approach and it requires modifications to oligonucleotides that can bind to RNA and DNA (refer to Appendix 2 for a description of cell structure, genes, DNA, RNA, and proteins). The antisense drugs are used to stop transcriptional (from DNA) or translational (from RNA) pathways from proceeding, and so interfere with the process of disease. 

Some lymphomas, for example, are related to overexpression of Bcl-2. Antisense oligonucleotides are specially designed to target the overexpression of Bcl-2. Oblimersen (Genasense) is an antisense drug by Genta to block Bcl-2 production and enhance the efficacy of other standard chemotherapy drugs such as paclitaxel, fludarabine, irinotecan, and cyclophosphamide. 

Currently, there is only one antisense drug on the market— Vitravene (active ingredient fomivirsen) for the treatment of cytomegalovirus (CMV)-induced retinitis (inflammation of the retina) in AIDS patients. Fomivirsen has 21 nucleotides complementary to a CMV mRNA sequence, which is necessary for the production of infectious virus. Two examples of experimental antisense drugs are provided in Exhibit 3.15, while Table 3.1 lists other antisense drugs in clinical phase. 

Another antisense drug, Genasense, was refused filing by the FDA for insufficient evidence to demonstrate its efficacy, although an appeal is ongoing from... 

A small number of biopharmaceuticals are delivered by nonparenteral means. Recombinant DNase is given by inhalation aerosol to reduce the viscosity of mucus in the lungs of patients with cystic hbrosis. A platelet-derived growth factor in the form of a gel is administered topically for wound healing. Several hormones and peptides are administered in solution by the intranasal route. A solution of an antisense drug used for the treatment of cytomegalovirus retinitis is injected directly into the eye. 

Penichet ML, et al. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting initial applications in anti-HIV antisense drug delivery to the brain. J Immunol 1999 163(8) 4421—4426. 

The first antisense drug Vitravene has now been approved for the treatment of patients with cytomegalovirus-induced... 

Crooke, S.T. (1999) Molecular mechanisms of action of antisense drugs. Antisense Biochim. Biophys. Acta., 1489, 31 14. 

Crooke, S.T. (2000a) Comments on evaluation of antisense drugs in the clinic. Antisense Nucleic Acid Drug Dev., 10, 225-227. 

Freier, S. (1993) Hybridization considerations affecting antisense drugs. In B.Lebleu and S.T.Crooke (eds.) Antisense Research and Applications. CRC, Boca Raton, pp. 67-82. 

Henderson-Hasselbalch equation 15. Antisense drugs target RNA. Why do they not target DNA ... 

Isis Pharmaceuticals Chemistry/Formulations, http // www.isispharm.com/Antisense-Technology/ Antisense-Drug-Discovery-Platform/Medicinal-Chemistry. htm (accessed August 2012). 

Figure 7.14 Development routes for antisense drugs. Examples of (a) a section of the backbone of a deoxyribonucleic chain, (b) backbone modifications, (c) sugar residue modifications and (d) base modifications...

What are antisense drugs How do they inhibit nucleic acids ... 

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