Neurodegenerative diseases of the central nervous system present with pathologies of chronic inflammation and reactive gliosis. Currently, our team explores approaches to hack reactive gliosis to promote neural regeneration. By utilizing methods to discover peptides that promote uptake and delivery via peripheral nerves and the autonomic nervous system, we engineer CNS targeting-ligands to enhance drug-delivery to neurons and sites of degeneration. Similarly, we employ gene-therapy and targeted genome-editing approaches to engineer tissues and direct neural stem cell differentiation within neurodegenerative models. As a result, our team has begun to develop methods to analyze single-cell transcriptomes to map the development, maturation, and persistence of cell-phenotypes within whole tissues as means to quantify how cell-populations respond to a treatment. Thus, we can analyze how diseased or gliotic tissues respond to stem cell therapies and genome editing to develop cutting-edge medicines that treat the degenerative or injured central nervous system.