Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer

  title={Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer},
  author={Brian D. Brown and Mary Anna Venneri and Anna Zingale and Lucia Sergi Sergi and Luigi Naldini},
  journal={Nature Medicine},
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by repressing translation of target cellular transcripts. Increasing evidence indicates that miRNAs have distinct expression profiles and play crucial roles in numerous cellular processes, although the extent of miRNA regulation is not well known. By challenging mice with lentiviral vectors encoding target sequences of endogenous miRNAs, we show the efficiency of miRNAs in sharply segregating gene expression among… 

Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state

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MicroRNA-regulated viral vectors for gene therapy.

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Novel Expression Vectors Enabling Induction of Gene Expression by Small-Interfering RNAs and MicroRNAs

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De-targeting by miR-143 decreases unwanted transgene expression in non-tumorigenic cells

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Positive Bioluminescence Imaging of MicroRNA Expression in Small Animal Models Using an Engineered Genetic-Switch Expression System, RILES.

Methods and protocols to monitor the expression of myomiR-206, -1, and -133 in the tibialis anterior muscle of mice and it is demonstrated that RILES is a specific, sensitive, and robust method to determine the fine-tuning of miRNA expression during the development of an experimental pathological process in mice.

MicroRNA Expression Differences in Human Hematopoietic Cell Lineages Enable Regulated Transgene Expression

Qualitative analysis of the miRNA profiles of peripheral blood cells identifies the circulating hematopoietic cellular miRNAs, supports the use of mi RNA profiles for distinguishing different hematOPoietIC lineages and suggests that endogenously expressed miRNAAs can be exploited to regulate transgene expression in a cell-specific manner.

A double-switch vector system positively regulates transgene expression by endogenous microRNA expression (miR-ON vector).

A strategy to couple transgene expression to the activity of the miR of interest and demonstrate its performance by live monitoring of two miRs in different stages of human primary hematopoietic stem/progenitor cell differentiation in vivo is described.



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MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression

A technique for visualizing detailed miRNA expression patterns in mouse embryos is reported, elucidate the tissue-specific expression of several miRNAs during embryogenesis, and negatively regulates Hoxb8 and miR-196a, indicating that its restricted expression pattern probably reflects a role in the patterning function of the Hox complex.

Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters

Synthetic bidirectional promoters are developed that mediate coordinate transcription of two mRNAs in a ubiquitous or a tissue-specific manner that enabled efficient dual gene transfer in several tissues in vivo after direct delivery or transgenesis, and in a human gene therapy model.

Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.

The results show that proximal pairs of miRNAs are generally coexpressed, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic mi RNAs.

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Principles of MicroRNA–Target Recognition

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The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution

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