期刊
VIROLOGY
卷 397, 期 2, 页码 337-345出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.11.021
关键词
Adenovirus; Gene; Expression; E2F-1; Truncated; Tet-Off; System; Apoptosis
类别
资金
- National Cancer Institute [R01CA129975, R01CA90784]
- Kentucky Lung Cancer Research Program [G030983, GMB081410]
- National Council of Science and Technology (CONACYT) of Mexico
Adenoviral vectors are highly efficient at transferring genes into cells and are broadly used in cancer gene therapy. However, many therapeutic genes are toxic to vector host cells and thus inhibit vector production. The truncated form of E2F-1 (E2Ftr), which lacks the transactivation domain, can significantly induce cancer cell apoptosis, but is also toxic to HEK-293 cells and inhibits adenovirus replication. To overcome this, we have developed binary- and single-vector systems with a modified tetracycline-off inducible promoter to control E2Ftr expression. We compared several vectors and found that the structure of expression cassettes in vectors significantly affects E2Ftr expression. One construct expresses high levels of inducible E2Ftr and efficiently causes apoptotic cancer cell death by activation of caspase-3. The approach developed in this study may be applied in other viral vectors for encoding therapeutic genes that are toxic to their host cells and/or inhibit vector propagation. (C) 2009 Elsevier Inc. All rights reserved.
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