Polynucleotide Inhibition Of RNA Destabilization And Sequestration


A variety of mechanisms are available in eukaryotic cells for regulating gene expression such that each gene product is produced at appropriate times and in appropriate quantities. It is well established that a significant amount of control over gene expression can be exerted at the level of RNA processing and RNA stability. Evidence exists that suggests a role for antisense RNA transcripts (countertranscripts) in RNA destabilization and nuclear sequestration which promotes down-regulation of protein expression. Countertranscript-RNAs are encoded by the complementary-strand of a gene, and they are sometimes found in different tissues or developmental stages than their corresponding sense or transcript-RNAs, and these different expression patterns yield different gene-product expression patterns. Therefore, transcript-countertranscript complexes can play a critical role in the degradation and sequestration of RNAs and thus affect protein expression. The disclosed invention provides a means whereby defined polynucleotides can be introduced into a cell or tissue in order to prevent transcript-countertranscript interactions and thereby inhibit this degradation and nuclear sequestration of transcript RNA. This methodology could enhance the expression of a target gene-product encoded by a transcript-RNA by preventing transcript-countertranscript association. The polynucleotides themselves can be introduced or expression vectors can be created containing the polynucleotide sequence in order to express the defined polynucleotides in the cells or tissue of choice. These polynucleotides can also be used in in vivo and ex vivo regimens. As an example, these polynucleotides could be used to treat tumorigenic cells in such a way as to promote the expression of known apoptotic proteins whereby the tumorigenic cells are selectively killed. In summary, this technology could be used in any number of applications where the promotion of the expression of a particular gene-product is desirable.

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Updated: Feb 1, 1999