Advances in Human Stem Cells and Genome Editing to Understand and Develop Treatment for Fragile X Syndrome

Fragile X syndrome (FXS), the most common genetic form of autism spectrum disorder, is caused by deficiency of the fragile X mental retardation protein (FMRP). Despite extensive research using animal models, understanding how FMRP regulates human brain development and function remains a major challenge. Human pluripotent stem cells (hPSCs) offer powerful platforms for studying mechanisms of human diseases and for evaluating potential treatments. Genome editing, particularly the CRISPR/Cas9-based method, is highly effective for generating models to study genetic human diseases. Here we summarize how hPSCs and genome editing provide much-needed models for studying the genetic underpinnings, cellular mechanisms, and neuropathology that are unique to human FXS. The use of hPSCs and genome editing also provides an essential platform for therapeutic development in FXS.