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Research Paper
Phi29 pRNA Vector for Efficient Escort of Hammerhead Ribozyme Targeting Survivin in Multiple Cancer Cells
Hongyun Liu, Songchuan Guo, Richard Roll, Jie Li, Zhijuan Diao, Ningsheng Shao, Mark R. Riley, Alexander M. Cole, J. Paul Robinson, Nicholas Snead, Guanxin Shen and Peixuan Guo
volume 6 | issue 5
May 2007Pages: 697 - 704
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Ribozymes are potential therapeutic agents which suppress specific genes in disease-affected cells. Ribozymes have high substrate cleavage efficiency, yet their medical application has been hindered by RNA degradation, aberrant cell trafficking, or misfolding when fused to a carrier. In this study, we constructed a chimeric ribozyme carried by the motor pRNA of bacteriophage phi29 to achieve proper folding and enhanced stability. A pRNA molecule contains an interlocking loop domain and a 5´/3´ helical domain, which fold independently of one another. When a ribozyme is connected to the helical domain, the chimeric pRNA/ribozyme reorganize into a circularly permuted form, in which the 5´/3´ ends are relocated and buried in the original 71′/75′ positions. Effective silencing of an anti-apoptotic gene survivin by an appropriately designed chimeric ribozyme, as demonstrated at mRNA and protein levels, led to programmed cell death in various human cancer cell lines, including breast, prostate, cervical, nasopharyngeal, and lung, without causing significant non-specific cytotoxicity. Through the interlocking interaction of right and left loops, monomer pRNA/ribozyme chimeras can be incorporated into multi-functional dimer, trimer and hexamer complexes for specific gene delivery. Using the phi29 motor pRNA as an escort may revive the ribozyme's strength in medical application again.
Authors
Hongyun Liu
Huazhong University of Science and Technology, Wuhan, China
Songchuan Guo
Purdue University, West Lafayette, Indiana
Richard Roll
Purdue University, West Lafayette, Indiana
Jie Li
National Institutes of Health, Bethesda, MD
Zhijuan Diao
Huazhong University of Science and Technology, Wuhan, China
Ningsheng Shao
Beijing Institute of Basic Medical Sciences, Beijing, China
Mark R. Riley
University of Arizona, Tucson, Arizona
Alexander M. Cole
University of Central Florida, Orlando, Florida
J. Paul Robinson
Purdue University, West Lafayette, Indiana
Nicholas Snead
Purdue University, West Lafayette, Indiana
Guanxin Shen
Huazhong University of Science and Technology, Wuhan, China
Peixuan Guo
Purdue University, West Lafayette, Indiana
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.