Document Detail


Progress toward oligonucleotide therapeutics: pharmacodynamic properties.
MedLine Citation:
PMID:  7682523     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although many issues remain to be resolved, recent progress suggests that oligonucleotides may have therapeutic potential. The first therapeutic oligonucleotide, ISIS 2105, an oligonucleotide designed to treat genital warts, has completed Phase I clinical trials and is undergoing Phase II testing. Conceptually, oligonucleotides may interact with nucleic acid or nonnucleic acid receptors; however, rational design of oligonucleotide drugs to interact with nucleic acid receptors is significantly simpler because the factors that determine affinity and selectivity are better understood. Recent progress demonstrates that this information can be coupled to rapid advances in the medicinal chemistry of oligonucleotides to create new generations of oligonucleotide drugs with dramatically improved properties. The purposes of this review are to place oligonucleotide therapeutics in the context of modern molecular drug discovery and to summarize progress in understanding the pharmacodynamic properties of oligonucleotides designed to bind to nucleic acid receptors. The pharmacokinetic and toxicologic properties of oligonucleotides have been reviewed recently (1-4). The activities of oligonucleotides that bind to nonnucleic acid receptors will be considered in future reviews.
Authors:
S T Crooke
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  7     ISSN:  0892-6638     ISO Abbreviation:  FASEB J.     Publication Date:  1993 Apr 
Date Detail:
Created Date:  1993-05-18     Completed Date:  1993-05-18     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  533-9     Citation Subset:  IM    
Affiliation:
Isis Pharmaceuticals, Carlsbad, California 92008.
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MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Oligonucleotides / metabolism,  pharmacology,  therapeutic use*
RNA / metabolism
Chemical
Reg. No./Substance:
0/Oligonucleotides; 63231-63-0/RNA

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