Antisense Oligonucleotides as Potential Therapeutics for Type 2 Diabetes
Suxiang Chen1,2, Nabayet Sbuh1,2, Rakesh N Veedu1,2
1Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Australia.
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.
Insights
Antisense oligonucleotides offer a novel approach to managing type 2 diabetes (T2D) by targeting disease-causing genes. This review explores their potential in treating hyperglycemia and insulin resistance.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Type 2 diabetes (T2D) is a chronic metabolic disorder marked by hyperglycemia due to insulin issues.
- Current treatments, like oral hypoglycemics, have limited efficacy and side effects, failing to halt disease progression.
- Antisense oligonucleotides (ASOs) show promise for T2D by downregulating disease-related gene expression.
Purpose of the Study:
- To comprehensively review antisense molecules developed for T2D treatment.
- To explore the potential of ASOs in suppressing genes linked to insulin resistance and hyperglycemia.
Main Methods:
- Literature review of antisense oligonucleotide research for T2D.
- Analysis of ASO mechanisms targeting disease-causing genes at RNA and protein levels.
- Examination of FDA-approved antisense agents for therapeutic applications.
Main Results:
- ASOs can effectively downregulate specific gene expression implicated in T2D.
- Seven ASO agents are currently FDA-approved for various human diseases.
- This approach offers a targeted strategy beyond conventional T2D therapies.
Conclusions:
- Antisense oligonucleotides represent a promising therapeutic strategy for T2D.
- Targeting gene expression offers a novel pathway for managing hyperglycemia and insulin resistance.
- Further research into ASOs could lead to advanced T2D prevention and treatment options.
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