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US 11,078,487 B2Granted
Cancer-specific trans-splicing ribozymes and use thereof
AssigneesRznomics Inc., Dong-A University Research Foundation for Industry-Academy Cooperation, Industry-Academic Cooperation Foundation, Dankook University
InventorsSeong-Wook Lee, Chang Ho Lee, Seung Ryul I Han, Ji Hyun Kim, Eun Yi Cho, Jin Sook Jeong, Mi Ha Ju
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Abstract
A cancer-specific trans-splicing ribozyme and a use thereof are disclosed. The trans-splicing ribozyme does not act on normal tissue, but is specifically expressed in cancer tissue. Therefore, it is very safe and has excellent expression efficiency at the post-transcription level, and thus can be effectively used in treatment of cancer.
Claims17
A nucleic acid construct, comprising, in the order from 5′ end to 3′ end:
- (i) a cytomegalovirus (CMV) promoter;
- (ii) a splicing donor/splicing acceptor sequence (SD/SA sequence);
- (iii) a ribozyme-desired gene expression cassette, which is operably linked to the CMV promoter (i), includes (a) a sequence encoding a trans-splicing ribozyme targeting a cancer-specific gene and (b) a target gene connected to a 3′ exon of the ribozyme-encoding sequence;
- (iv) a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE);
- and
- (v) a nucleic acid sequence complementary to microRNA-122 (miR-122), said nucleic acid sequence (v) being connected to the 3′ end of the WPRE and comprising one or more copies of the nucleic acid sequence of SEQ ID NO:
- 5,
- wherein the SD/SA sequence is connected to the 5′ end of the ribozyme-desired gene expression cassette, and the WPRE is connected to the 3′ end of the ribozyme-desired gene expression cassette, and
- wherein the cancer-specific gene is a telomerase reverse transcriptase (TERT) mRNA sequence.
6 more elements
Dependencies are inferred from the claim text.