Details:

Alternative Title:
ACS Synth Biol
Publisher's site:
http://dx.doi.org/10.1021/acssynbio.5b00040
Personal Author:
Sayeg, Marianna K. ; Weinberg, Benjamin H. ; Cha, Susie S. ; Goodloe, Michael ; Wong, Wilson W. ; ... More +
Sayeg, Marianna K. ; Weinberg, Benjamin H. ; Cha, Susie S. ; Goodloe, Michael ; Wong, Wilson W. ; Han, Xue ; Less -
Description:
Targeting transgene expression to specific cell types in vivo has proven instrumental in characterizing the functional role of defined cell populations. Genetic classifiers, synthetic transgene constructs designed to restrict expression to particular classes of cells, commonly rely on transcriptional promoters to define cellular specificity. However, the large size of many natural promoters complicates their use in viral vectors, an important mode of transgene delivery in the brain and in human gene therapy. Here, we expanded upon an emerging classifier platform, orthogonal to promoter-based strategies, that exploits endogenous microRNA regulation to target gene expression. Such classifiers have been extensively explored in other tissues; however, their use in the nervous system has thus far been limited to targeting gene expression between neurons and supporting cells. Here, we tested the possibility of using combinatory microRNA regulation to specify gene targeting between neuronal subtypes, and successfully targeted inhibitory cells in the neocortex. These classifiers demonstrate the feasibility of designing a new generation of microRNA-based neuron-type- and brain-region-specific gene expression targeting neurotechnologies.
Subject:
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Article
Gene Therapy
Genetic Classifier
Inhibitory Neurons
MicroRNA
Neuroengeineering
Synthetic Biology

Source:
ACS Synth Biol. 4(7):788-795.
Pubmed ID:
25848814
Pubmed Central ID:
PMC4547530
Document Type:
Journal Article ;
Funding:
1DP2CA186574/CA/NCI NIH HHS/United States ; 1DP2NS082126/DP/NCCDPHP CDC HHS/United States ; 1R01NS081716/NS/NINDS NIH HHS/United States ; 1R01NS087950/NS/NINDS NIH HHS/United States ; 1R21NS078660/NS/NINDS NIH HHS/United States ; ... More +
1DP2CA186574/CA/NCI NIH HHS/United States ; 1DP2NS082126/DP/NCCDPHP CDC HHS/United States ; 1R01NS081716/NS/NINDS NIH HHS/United States ; 1R01NS087950/NS/NINDS NIH HHS/United States ; 1R21NS078660/NS/NINDS NIH HHS/United States ; 5R00MH085944/MH/NIMH NIH HHS/United States ; DP2 NS082126/NS/NINDS NIH HHS/United States ; R00 MH085944/MH/NIMH NIH HHS/United States ; R01 NS087950/NS/NINDS NIH HHS/United States ; R21 NS078660/NS/NINDS NIH HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:b10fbb6e0ab990533484fe20d2860d85ba0478713ceb7b88acc9c0e46642ccdb
File Type:

Supporting Files

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