Antisense Oligonucleotides as Potential Therapeutics for Type 2 Diabetes

Nucleic Acid Ther. 2021 Feb;31(1):39-57. doi: 10.1089/nat.2020.0891. Epub 2020 Oct 7.

Abstract

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from inefficient signaling and insufficient production of insulin. Conventional management of T2D has largely relied on small molecule-based oral hypoglycemic medicines, which do not halt the progression of the disease due to limited efficacy and induce adverse effects as well. To this end, antisense oligonucleotide has attracted immense attention in developing antidiabetic agents because of their ability to downregulate the expression of disease-causing genes at the RNA and protein level. To date, seven antisense agents have been approved by the United States Food and Drug Administration for therapies of a variety of human maladies, including genetic disorders. Herein, we provide a comprehensive review of antisense molecules developed for suppressing the causative genes believed to be responsible for insulin resistance and hyperglycemia toward preventing and treating T2D.

Keywords: antisense oligonucleotides; gene silencing; hyperglycemia; insulin resistance; oligonucleotide therapeutics; type 2 diabetes.

Publication types

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

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Genetic Therapy*
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / genetics
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance / genetics
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / therapeutic use*

Substances

  • Hypoglycemic Agents
  • Oligonucleotides, Antisense