Variations in mRNA content have no effect on the potency of antisense oligonucleotides.
Antisense Nucleic Acid Drug Dev
; 10(6): 453-61, 2000 Dec.
Article
in En
| MEDLINE
| ID: mdl-11198929
ABSTRACT
A fundamental question with regard to antisense pharmacology is the extent to which RNA content or transcription rate or both affect the potency of antisense drugs. We have addressed this by controlling RNA content and transcription rate using either an exogenous gene expressed after transfection or an endogenous gene induced with a cytokine. We have demonstrated that in both A549 and HeLa cells, varying RNA copy numbers from <1 to >100 copies per cell has no effect on the potency of RNase H-active antisense drugs transfected into cells, nor did variation in transcription rate have an effect on potency. We demonstrate that this is because the number of oligonucleotide molecules per cell is vastly in excess of the RNA copy number. These data further suggest that a significant fraction of cell-associated antisense drug molecules may be unavailable to interact with the target RNA, an observation that is not surprising, as phosphorothioate oligonucleotides interact with many cellular proteins. We suggest that these data may extrapolate to in vivo results.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Gene Expression
/
Oligonucleotides, Antisense
Limits:
Humans
Language:
En
Journal:
Antisense Nucleic Acid Drug Dev
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
FARMACOLOGIA
Year:
2000
Document type:
Article
Affiliation country:
Estados Unidos