title: In vivo identification of therapeutic constructs from pooled candidates in HD model mice.
abstract: Rapidly identifying targets for Huntington's Disease (HD) therapeutics in relevant mouse models could hasten the development of patient interventions. We have recently described a method for rapidly and quantitatively measuring the progression of HD-like symptoms in mouse models. Because this method uses flow cytometry to measure GFP levels in affected neurons, it is amenable to pooled approaches. Here we describe a continuation of this work, using pools of shRNA-delivering AAV vectors and high throughput sequencing to determine which hairpins in a mixed population are most effective at preventing the transcriptional dysregulation phenotype of R6/2 mice.
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Zachary R
authors: ZR
authors: Crook
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: David E
authors: DE
authors: Housman
mesh_terms: D000818:Animals; D000229:Dependovirus; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D049452:Green Fluorescent Proteins
keywords: Huntington's Disease; Neurodegeneration; gene expression; neuroprotection; pooled screening; viral vectors