Rationally Designed MicroRNA-Based Genetic Classifiers Target Specific Neurons in the Brain

Details

• Alternative Title:
  ACS Synth Biol
• Personal Author:
  Sayeg, Marianna K. ; Weinberg, Benjamin H. ; Cha, Susie S. ; Goodloe, Michael ; Wong, Wilson W. ; Han, Xue
• 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.
• Subjects:
  Animals Article Brain Gene Therapy Genetic Classifier Genetic Vectors Green Fluorescent Proteins Inhibitory Neurons Lentivirus Mice MicroRNA MicroRNAs Microscopy, Confocal Neuroengeineering Neurons Synthetic Biology

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• Source:
  ACS Synth Biol. 4(7):788-795
• Pubmed ID:
  25848814
• Pubmed Central ID:
  PMC4547530
• Document Type:
  Journal Article
• Funding:
  1R01NS081716/NS/NINDS NIH HHSUnited States/ ; 1R01NS087950/NS/NINDS NIH HHSUnited States/ ; 1DP2NS082126/DP/NCCDPHP CDC HHSUnited States/ ; DP2 NS082126/NS/NINDS NIH HHSUnited States/ ; R01 NS087950/NS/NINDS NIH HHSUnited States/ ; R00 MH085944/MH/NIMH NIH HHSUnited States/ ; 5R00MH085944/MH/NIMH NIH HHSUnited States/ ; 1DP2CA186574/CA/NCI NIH HHSUnited States/ ; R01 NS081716/NS/NINDS NIH HHSUnited States/ ; DP2 CA186574/CA/NCI NIH HHSUnited States/ ; R21 NS078660/NS/NINDS NIH HHSUnited States/ ; 1R21NS078660/NS/NINDS NIH HHSUnited States/
• Volume:
  4
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b10fbb6e0ab990533484fe20d2860d85ba0478713ceb7b88acc9c0e46642ccdb
• Download URL:
  https://stacks.cdc.gov/view/cdc/34414/cdc_34414_DS1.pdf
• File Type:
  [PDF - 968.88 KB ]