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| AN ASSESSMENT OF THE ANTISENSE PROPERTIES OF RNASE H-COMPETENT AND STERIC-BLOCKING OLIGOMERS |
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| Author(s): BONHAM MA, BROWN S, BOYD AL, BROWN PH, BRUCKENSTEIN DA, HANVEY JC, THOMSON SA, PIPE A, HASSMAN F, BISI JE, FROEHLER BC, MATTEUCCI MD, WAGNER RW, NOBLE SA, BABISS LE |
| Source: NUCLEIC ACIDS RESEARCH Volume: 23 Issue: 7 Pages: 1197-1203 Published: APR 11 1995 |
| Times Cited: 126 References: 21 |
| Abstract: The antisense activity and gene specificity of two classes of oligonucleotides (ONs) were directly compared in a highly controlled assay. One class of ONs has been proposed to act by targeting the degradation of specific RNAs through an RNase H-mediated mechanism and consists of C-5 propynyl pyrimidine phosphorothioate ONs (propyne-S-ON). The second class of antisense agents has been proposed to function by sterically blocking target RNA formation, transport or translation and includes sugar modified (2'-O-allyl) ONs and peptide nucleic acids (PNAs). Using a CV-1 cell based microinjection assay, we targeted antisense agents representing both classes to various cloned sequences localized within the SV40 large T antigen RNA. We determined the propyne-S-ON was the most potent and gene-specific agent of the two classes which likely reflected its ability to allow RNase H cleavage of its target. The RNA oligomer inhibited T Ag expression via an antisense mechanism, but was less effective than the propyne-S-ON; the lack of potency may have been due in part to the PNAs slow kinetics of RNA association. interestingly, unlike the 2'-O-allyl ON, the antisense activity of the PNA was not restricted to the 5' untranslated region of the T Ag RNA. Based on these findings we conclude that PNAs could be effective antisense agents with additional chemical modification that will lead to more rapid association with their RNA target. |
| Document Type: Article |
| Language: English |
Addresses:
1. GLAXO INC, RES INST, DEPT MOLEC CELL BIOL, RES TRIANGLE PK, NC 27709 USA
2. GLAXO INC, RES INST, DEPT MED CHEM, RES TRIANGLE PK, NC 27709 USA
3. GLAXO INC, RES INST, DEPT MOLEC SCI, RES TRIANGLE PK, NC 27709 USA
4. HOOD COLL, DEPT BIOL, FREDERICK, MD 21710 USA
5. GILEAD SCI, FOSTER CITY, CA 94404 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: QW317 |
| ISSN: 0305-1048 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |