中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus

文献类型:期刊论文

作者Hoeprich, S; Zhou, Q; Guo, S; Shu, D; Qi, G; Wang, Y; Guo, P
刊名GENE THERAPY
出版日期2003
卷号10期号:15页码:1258-1267
关键词pRNA of bacteriophage phi29 hammerhead fibozyme gene therapy nanomotor DNA packaging hexamer
通讯作者Guo, P (reprint author), Purdue Univ, Purdue Canc Res Ctr, Dept Pathobiol, B-36 Hansen Life Sci Res Bldg, W Lafayette, IN 47907 USA.,
英文摘要The DNA-packaging pRNA of bacterial virus phi29, which forms dimers and then hexamers, contains two independent tightly self-folded domains. Circularly permuted pRNAs were constructed without impacting pRNA folding. Connecting the pRNA 5'/3' ends with variable sequences did not disturb its folding and function. These unique features, which help prevent two common problems - exonuclease degradation and misfolding in the cell, make pRNA an ideal vector to carry therapeutic RNAs. A pRNA-based vector was designed to carry hammerhead ribozymes that cleave the hepatitis B virus (HBV) polyA signal. The chimeric HBV-targeting ribozyme was connected to the pRNA 5'/3' ends as circularly permuted pRNA. Two cis-cleaving ribozymes were used to flank and process the chimeric ribozyme. The hammerhead ribozyme including its two arms for HBV targeting was able to fold correctly while escorted by the pRNA. The chimeric ribozyme cleaved the polyA signal of HBV mRNA in vitro almost completely. Cell culture studies showed that the chimeric ribozyme was able to enhance the inhibition of HBV replication when compared with the ribozyme not escorted by pRNA, as demonstrated by Northern blot and e-antigen assays. pRNA could also carry another hammerhead ribozyme to cleave other RNA substrate. These findings suggest that pRNA can be used as a vector for imparting stability to ribozymes, antisense, and other therapeutic RNA molecules in vivo.
学科主题Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine
类目[WOS]Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
关键词[WOS]DNA PACKAGING MOTOR ; PHAGE PHI-29 ; BACTERIOPHAGE-PHI-29 DNA ; CHEMICAL MODIFICATION ; VIRAL-RNA ; SEQUENCE REQUIREMENT ; RIBONUCLEASE-P ; HEXAMERIC RNA ; PROHEAD RNA ; IN-VITRO
收录类别SCI
语种英语
WOS记录号WOS:000184207000008
版本出版稿
源URL[http://202.127.25.143/handle/331003/2375]  
专题上海生化细胞研究所_上海生科院生化细胞研究所
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GB/T 7714
Hoeprich, S,Zhou, Q,Guo, S,et al. Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus[J]. GENE THERAPY,2003,10(15):1258-1267.
APA Hoeprich, S.,Zhou, Q.,Guo, S.,Shu, D.,Qi, G.,...&Guo, P.(2003).Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus.GENE THERAPY,10(15),1258-1267.
MLA Hoeprich, S,et al."Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus".GENE THERAPY 10.15(2003):1258-1267.

入库方式: OAI收割

来源:上海生物化学与细胞生物学研究所

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