Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research

Front Endocrinol (Lausanne). 2020 Oct 8;11:576632. doi: 10.3389/fendo.2020.576632. eCollection 2020.

Abstract

The inheritance of variants that lead to coding changes in, or the mis-expression of, genes critical to pancreatic beta cell function can lead to alterations in insulin secretion and increase the risk of both type 1 and type 2 diabetes. Recently developed clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) gene editing tools provide a powerful means of understanding the impact of identified variants on cell function, growth, and survival and might ultimately provide a means, most likely after the transplantation of genetically "corrected" cells, of treating the disease. Here, we review some of the disease-associated genes and variants whose roles have been probed up to now. Next, we survey recent exciting developments in CRISPR/Cas9 technology and their possible exploitation for β cell functional genomics. Finally, we will provide a perspective as to how CRISPR/Cas9 technology may find clinical application in patients with diabetes.

Keywords: beta cell; genome editing; genome-wide association studies; maturity onset of diabetes of the young; mouse models; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CRISPR-Cas Systems*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / therapy*
  • Gene Deletion*
  • Gene Editing*
  • Genetic Therapy*
  • Genomics / methods*
  • Humans
  • Insulin-Secreting Cells / metabolism*