Methods for controlling cell-type by dedifferentiation, directed differentiation, and transdifferentiation or "direct reprogramming" have enabled the generation, in the laboratory, of tissue-specific, patient-specific cells from small, non-invasive skin samples. However, critical roadblocks have so far prevented these methods from being used to generate large screening libraries. Existing cell-reprogramming technologies are slow and inefficient, using either integrating viruses, which carry risks of insertional mutagenesis and spontaneous oncogene reactivation, or non-viral vectors with even lower efficiencies. Factor Bioscience has developed the first rapid, reliable, DNA-free technology for reprogramming adult cells. In this project, we will apply this technology to generate a library of cells capable of generating neurons from patients with and without Alzheimer's disease. Furthermore, we will use our patented gene-editing technology to confer Alzheimer's- associated mutations to healthy patient samples, creating the first isogenic library for screening drugs to treat or preven Alzheimer's disease.
Public Health Relevance: This project will develop the first library of gene-edited neurons developed from patient cells in order to model Alzheimer's-disease-associated mutations in an isogenic background. The results of this project will enable more accurate drug screening for the treatment and prevention of Alzheimer's disease.
Public Health Relevance Statement: This project will develop the first library of gene-edited neurons developed from patient cells in order to model Alzheimer's-disease-associated mutations in an isogenic background. The results of this project will enable more accurate drug screening for the treatment and prevention of Alzheimer's disease.
NIH Spending Category: Aging; Alzheimer's Disease; Biotechnology; Brain Disorders; Genetics; Neurodegenerative; Neurosciences; Prevention; Stem Cell Research
Project Terms: Adult; Alzheimer disease prevention; Alzheimer disease screening; Alzheimer's Disease; Alzheimer's disease model; American; Amyloid; APP gene; base; Biological Assay; Caring; Cell Therapy; cell type; Cells; cost; design; Disease; DNA; DNA Repair; DNA Viruses; Enzyme-Linked Immunosorbent Assay; Etiology; Fibroblasts; Gene Library; Generations; Genes; Genetic; Human; in vitro Model; induced pluripotent stem cell; Insertional Mutagenesis; Laboratories; Legal patent; Libraries; Literature; Measurement; Measures; Messenger RNA; Methods; Modification; Molecular Cloning; Mutation; Neurodegenerative Disorders; Neurons; Non-Viral Vector; nuclease; Oncogenes; Parkinson Disease; Patients; Phase; pluripotency; Pluripotent Stem Cells; Preclinical Drug Evaluation; Presenile Alzheimer Dementia; presenilin-1; Prevalence; prevent; Problem Solving; Process; PS2 protein (alzheimer-associated); Rattus; repaired; Research; Ribonucleases; Risk; RNA; RNA chemical synthesis; Sampling; Screening procedure; Skin; Speed (motion); Staining method; Stains; tau phosphorylation; Techniques; Technology; Tissues; Transcription Coactivator; transdifferentiation; Tubulin; Virus
