Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent...Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.展开更多
The Loess Plateau is an earthquake prone region of China, where the effects of loess deposit on ground motion were discovered during the 2008 Wenchuan earthquake(Ms8.0) and the 2013 Minxian-Zhangxian earthquake(Ms6.6)...The Loess Plateau is an earthquake prone region of China, where the effects of loess deposit on ground motion were discovered during the 2008 Wenchuan earthquake(Ms8.0) and the 2013 Minxian-Zhangxian earthquake(Ms6.6). The field investigations, observations, and analyses indicated that large number of casualties and tremendous economic losses were caused not only by collapse and damage of houses with poor seismic performance, landslides, but also amplification effects of site conditions, topography and thickness of loess deposit, on ground motion. In this paper, we chose Dazhai Village and Majiagou Village as the typical loess site affected by the two earthquakes for intensity evaluation, borehole exploration, temporary strong motion array, micro tremor survey, and numerical analysis. The aim is to explore the relations between amplification factors and site conditions in terms of topography and thickness of loess deposit. We also developed site amplification factors of ground motion for engineering design consideration at loess sites. The results showed that the amplification effects are more predominant with increase in thickness of loess deposit and slope height. The amplification mayincrease seismic intensity by 1 degree, PGA and predominant period by 2 times, respectively.展开更多
基金Supported by The Deutsche Forschungsgemeinschaft,Nos.FE785/2-2 and FE785/4-1the Bundesministerium für Bildung und Entwicklung,No.031A331
文摘Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.
基金financially supported by National Natural Science Foundation of China (No.51478444 & No.41472297)
文摘The Loess Plateau is an earthquake prone region of China, where the effects of loess deposit on ground motion were discovered during the 2008 Wenchuan earthquake(Ms8.0) and the 2013 Minxian-Zhangxian earthquake(Ms6.6). The field investigations, observations, and analyses indicated that large number of casualties and tremendous economic losses were caused not only by collapse and damage of houses with poor seismic performance, landslides, but also amplification effects of site conditions, topography and thickness of loess deposit, on ground motion. In this paper, we chose Dazhai Village and Majiagou Village as the typical loess site affected by the two earthquakes for intensity evaluation, borehole exploration, temporary strong motion array, micro tremor survey, and numerical analysis. The aim is to explore the relations between amplification factors and site conditions in terms of topography and thickness of loess deposit. We also developed site amplification factors of ground motion for engineering design consideration at loess sites. The results showed that the amplification effects are more predominant with increase in thickness of loess deposit and slope height. The amplification mayincrease seismic intensity by 1 degree, PGA and predominant period by 2 times, respectively.
