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Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state
- Source :
- Nature Biotechnology, Nature Biotechnology, 2007, 25 (12), pp.1457-1467. ⟨10.1038/nbt1372⟩
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
Abstract
- We have shown previously that transgene expression can be suppressed in hematopoietic cells using vectors that are responsive to microRNA (miRNA) regulation. Here we investigate the potential of this approach for more sophisticated control of transgene expression. Analysis of the relationship between miRNA expression levels and target mRNA suppression suggested that suppression depends on a threshold miRNA concentration. Using this information, we generated vectors that rapidly adjust transgene expression in response to changes in miRNA expression. These vectors sharply segregated transgene expression between closely related states of therapeutically relevant cells, including dendritic cells, hematopoietic and embryonic stem cells, and their progeny, allowing positive/negative selection according to the cells' differentiation state. Moreover, two miRNA target sites were combined to restrict transgene expression to a specific cell type in the liver. Notably, the vectors did not detectably perturb endogenous miRNA expression or regulation of natural targets. The properties of miRNA-regulated vectors should allow for safer and more effective therapeutic applications.
- Subjects :
- [SDV.BIO]Life Sciences [q-bio]/Biotechnology
Transgene
Biomedical Engineering
Bioengineering
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Applied Microbiology and Biotechnology
microRNA
Gene expression
Animals
Humans
Gene Silencing
Transgenes
Vector (molecular biology)
ComputingMilieux_MISCELLANEOUS
Regulation of gene expression
Stem Cells
Gene Expression Regulation, Developmental
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Cell Differentiation
Dendritic cell
Embryonic stem cell
Molecular biology
Cell biology
MicroRNAs
Gene Targeting
Molecular Medicine
Stem cell
Biotechnology
Subjects
Details
- ISSN :
- 15461696 and 10870156
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Nature Biotechnology
- Accession number :
- edsair.doi.dedup.....dfb62dfa723ba6820b5a2cabed220fb9