@article{182f512392dd443f9a748e38a08fb05d,
title = "Phi29 pRNA vector for efficient escort of hammerhead ribozyme targeting survivin in multiple cancer cells",
abstract = "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 escorted 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 reorganizes into a circularly permuted form, and the 5′/3′ ends are relocated and buried in the original 71′/75′ positions. Effective silencing of the 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.",
keywords = "Bacteriophage phi29, Gene therapy, Nanomotor, Ribozyme, pRNA",
author = "Hongyun Liu and Songchuan Guo and Richard Roll and Jie Li and Zhijuan Diao and Ningsheng Shao and Riley, {Mark R.} and Cole, {Alexander M.} and Robinson, {J. Paul} and Snead, {Nicholas M.} and Guanxin Shen and Peixuan Guo",
note = "Funding Information: carry the RNA complex for cellular entry. The remaining subunits could be modified to carry specific therapeutic siRNAs, ribozymes, antisense RNAs, chemotherapy drugs, fluorescent dyes, heavy metals, quantum dots, or radioisotopes for cancer cell elimina‑ tion or detection. Endosome‑disrupting chemicals may also be incorporated into the RNA complex to promote the release of RNA from the endosome. In addition, the use of these RNA References nanoparticles (with sizes of 30–40 nanometers) avoids the problem 1. Forster AC, Symons RH. Self‑cleavage of virusoid of a short half‑life encountered in vivo by smaller molecules due 2. Sarver NA, Cantin EM, Chang PS, Zaia JA, Ladne PA, Stephens DA, Rossi JJ. Ribozymes 55‑ nucleotide active site. Cell 1987; 50:9‑16. to short retention times and also avoids the problem of poor as potential anti‑HIV‑1 therapeutic agents. Science 1990; 247:1222‑5. delivery efficiency encountered by larger molecules (greater than 3. Chowrira BM, Berzal‑Herranz A, Burke JM. Novel guanosine requirement for catalysis by 100 nanometers). It has been well accepted that immunogenicity the hairpin ribozyme. Nature 1991; 354:320‑2. of RNA is very low, except when complexed with protein.52The 4. Coleman J, Hirashima A, Inocuchi Y, Green PJ, Inouye M. A novel immune system against {\textcopyright}2007 LANDES BIOSCIENCE5.Knecht DA, Loomis WF. Antisense RNA inactivation of myosin heavy chain gene expres‑ immune response, which could allow long‑term administration. sion in Dictyostelium discoideum. Science 1987; 236:1081‑6. Acknowledgements Science 2002; 296:1319‑21.6.Li H, Li WX, Ding SW. Induction and suppression of RNA silencing by an animal virus. This work was mainly supported by NIH grant EB00370 Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering (Nanosciences and Nanotechnology in Biology and Medicine), and RNAs in mammalian cells. Science 2002; 296:550‑3. partially by DOD prostate cancer grant W81XWH‑05‑1‑0158 to Nature 2002; 418:435‑8.Jacque JM, Triques K, Stevenson M. Modulation of HIV‑1 replication by RNA interference. P.Guo, and the Hi‑tech research and development program of China (No. 2006AA02Z158) to G.X. Shen. We would like to thank Huifen Zhu and Zhihui Liang for the flow cytometry assays. Note Supplemental material can be found at: www.landesbioscience.com/supplement/LiuCBT6‑5‑sup.pdf",
year = "2007",
month = may,
doi = "10.4161/cbt.6.5.3962",
language = "English (US)",
volume = "6",
pages = "697--704",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Taylor and Francis Ltd.",
number = "5",
}