Rationally Designed MicroRNA-Based Genetic Classifiers Target Specific Neurons in the Brain
Year: 2015
Type: article
Abstract: 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.
Source: ACS Synthetic Biology
Institution: Boston University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Michael J. Fox Foundation for Parkinson's Research, Brain and Behavior Research Foundation, Pew Charitable Trusts, Alfred P. Sloan Foundation, National Institutes of Health, National Institute of Mental Health, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Center for Chronic Disease Prevention and Health Promotion
Awards: CRCNS: Propagation of beta oscillations in cortico-basal ganglia-thalamic loop, Causal Analysis of Electrically Connected Neural Networks, Light-Actuatable NanoRobots for Molecular Uncaging, G4998381234, G5237662773, Striatal Origin of Pathological Beta Oscillations in Parkinson's Disease, Cross Region Neural Computation Subserving Attention, Synthetically Reengineered T cells as the Next Generation of Smart Cancer Therapy, G8658647092
OpenAlex ID: W2069511920