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

Paper ID Volume ID Publish Year Pages File Format Full-Text
23671 43461 2012 6 PDF Available
Title
Selective regression of cancer cells expressing a splicing variant of AIMP2 through targeted RNA replacement by trans-splicing ribozyme
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.

► Trans-splicing ribozyme specific to AIMP2-DX2, a splicing variant of AIMP2. ► Specific RNA replacement with new transcript exerting therapeutic activity. ► Specific RNA replacement via high-fidelity trans-splicing in the AIMP2-DX2(+) cells. ► Specific and effective growth retardation of the AIMP2-DX2(+) lung cancer cells.

Keywords
Alternative splicing; AIMP2-DX2; Cancer gene therapy; Group I intron; RNA replacement; Trans-splicing ribozyme
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Selective regression of cancer cells expressing a splicing variant of AIMP2 through targeted RNA replacement by trans-splicing ribozyme
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 158, Issues 1–2, 31 March 2012, Pages 44–49
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us