Genome editing in stem cells for genetic neurodisorders

Prog Mol Biol Transl Sci. 2021:182:403-438. doi: 10.1016/bs.pmbts.2020.12.006. Epub 2021 Jan 30.

Abstract

The recent advent of genome editing techniques and their rapid improvement paved the way in establishing innovative human neurological disease models and in developing new therapeutic opportunities. Human pluripotent (both induced or naive) stem cells and neural stem cells represent versatile tools to be applied to multiple research needs and, together with genomic snip and fix tools, have recently made possible the creation of unique platforms to directly investigate several human neural affections. In this chapter, we will discuss genome engineering tools, and their recent improvements, applied to the stem cell field, focusing on how these two technologies may be pivotal instruments to deeply unravel molecular mechanisms underlying development and function, as well as disorders, of the human brain. We will review how these frontier technologies may be exploited to investigate or treat severe neurodevelopmental disorders, such as microcephaly, autism spectrum disorder, schizophrenia, as well as neurodegenerative conditions, including Parkinson's disease, Huntington's disease, Alzheimer's disease, and spinal muscular atrophy.

Keywords: Disease modeling; Genome editing; Human iPSCs; Neural stem cells; Neurodegenerative diseases; Neurodevelopmental disorders; Neurons; Neuropsychiatric disorders.

MeSH terms

  • Autism Spectrum Disorder*
  • Gene Editing
  • Humans
  • Induced Pluripotent Stem Cells*
  • Neural Stem Cells*
  • Neurodegenerative Diseases*