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Selective regression of cancer cells expressing a splicing variant of AIMP2 through targeted RNA replacement by trans-splicing ribozyme.

Journal of biotechnology (2012-01-31)
You-Sub Won, Seong-Wook Lee
ABSTRACT

AIMP2/p38 is a scaffolding protein critical for the assembly of the macromolecular tRNA synthetase complex. Moreover, AIMP2 harbors anti-proliferative activity and promotes cell death as a proapototic factor. A splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is specifically generated by an alternative splicing process and is highly expressed in human lung cancer cells and the tissues of cancer patients. AIMP2-DX2 induces tumorigenesis by compromising the tumor suppressor function of normal AIMP2. Here, we describe a novel approach to cancer therapy that is based on trans-splicing ribozyme-mediated replacement of specific RNAs. We developed a specific ribozyme that can target and replace the splicing variant AIMP2-DX2 RNA with a new transcript selectively exerting therapeutic activity in AIMP2-DX2-expressing lung cancer cells. The RNA replacement was employed via a high-fidelity trans-splicing reaction with the targeted residue of the AIMP2-DX2 transcript, but not with normal AIMP2 RNA, in the cells. Noticeably, the ribozyme could selectively deliver the activity of a suicide gene into the AIMP2-DX2 RNA expressing lung cancer cells and thereby specifically and effectively retard the growth of the cancer cells with prodrug treatment. Therefore, the AIMP2-DX2 RNA-targeting trans-splicing ribozyme could be a useful genetic agent for efficient therapy targeting lung cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-JTV1 antibody produced in mouse, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-AIMP2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab2