Shrna and sirna and mirna expression in a living organism under control of a codon-optimized repressor gene
AssigneeArtemis Pharmaceuticals GmbH
InventorsJost SEIBLER, Frieder SCHWENK, Birgit KUTER-LUKS, Michael BADER, Katarina KOTNIK
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Abstract
The present invention relates to a biological entity, notably a rat, carrying a regulator construct comprising a specific repressor gene and a responder construct comprising at least one segment corresponding to a short hairpin RNA (shRNA) or corresponding to complementary short interfering RNA (siRNA) strands or corresponding to miRNA, said at least one segment being under control of a promoter which contains an operator sequence corresponding to the repressor. The invention further relates to a method for preparing said biological entity and its use.
Claims45
A biological entity selected from the group consisting of a rat, a tissue culture derived from a rat or one or more cells of a cell culture derived from a rat, said biological entity carrying
- (i) a responder construct comprising at least one segment corresponding to a short hairpin RNA (shRNA) or to complementary short interfering RNA (siRNA) strands or to miRNA, said segment being under control of a ubiquitous promoter, wherein said promoter contains at least one operator sequence, by which said promoter is perfectly and ubiquitously regulatable by a repressor;
- and
- (ii) a regulator construct comprising a codon-optimized repressor gene, which provides for perfect regulation of the promoter of the responder construct, wherein the responder construct and/or the regulator construct is (are) stably integrated into the genome of the biological entity.
A method for preparing a biological entity selected from the group consisting of a rat, a tissue culture derived from a rat, or one or more cells of a cell culture derived from a rat, said biological entity carrying
- (i) a responder construct comprising at least one segment corresponding to a short hairpin RNA (shRNA) or to complementary short interfering RNA (siRNA) strands or to miRNA, said segment being under control of a ubiquitous promoter, wherein said promoter contains at least one operator sequence, by which said promoter is perfectly and ubiquitously regulatable by a repressor;
- and
- (ii) a regulator construct comprising a codon-optimized repressor gene, which provides for perfect regulation of the promoter of the responder construct, wherein the responder construct and/or the regulator construct is (are) stably integrated into the genome of the biological entity,
- which method comprises stably integrating said responder construct and said regulator construct into the genome of the biological entity.
Dependencies are inferred from the claim text.