Abstract
Diabetes mellitus (D.M.) is a common metabolic disorder caused mainly by combining two primary factors, which are (1) defects in insulin production by the pancreatic β-cells and (2) responsiveness of insulin-sensitive tissues towards insulin. Despite the rapid advancement in medicine to suppress elevated blood glucose levels (hyperglycemia) and insulin resistance associated with this hazard, a demand has undoubtedly emerged to find more effective and curative dimensions in therapeutic approaches against D.M. The administration of diabetes treatment that emphasizes insulin production and sensitivity may result in unfavorable side effects, reduced adherence, and potential treatment ineffectiveness. Recent progressions in genome editing technologies, for instance, in zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR-Cas)-associated nucleases, have greatly influenced the gene editing technology from concepts to clinical practices. Improvements in genome editing technologies have also opened up the possibility to target and modify specific genome sequences in a cell directly. CRISPR/Cas9 has proven effective in utilizing ex vivo gene editing in embryonic stem cells and stem cells derived from patients. This application has facilitated the exploration of pancreatic beta-cell development and function. Furthermore, CRISPR/Cas9 enables the creation of innovative animal models for diabetes and assesses the effectiveness of different therapeutic strategies in treating the condition. We, therefore, present a critical review of the therapeutic approaches of the genome editing tool CRISPR-Cas9 in treating D.M., discussing the challenges and limitations of implementing this technology.
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Abbreviations
- CRISPR:
-
Clustered regularly interspaced short palindromic repeats
- CrRNA:
-
CRISPR RNA
- D.M.:
-
Diabetes mellitus
- DSB.:
-
Double-strand break
- DSBR:
-
Double-strand break repair
- G.D.M.:
-
Gestational diabetes mellitus
- GWAS:
-
Genome-wide association studies
- HDR:
-
Homology direct repair
- hiPSCs:
-
Human embryonic stem cells
- hiPSCs:
-
Human induced pluripotent stem cells
- hPSCs:
-
Human pluripotent stem cells
- H.R.:
-
Homologous recombination
- LADA:
-
Latent autoimmune diabetes of adults
- NDM:
-
Neonatal diabetes mellitus
- NHEJ:
-
Non-homologous end joining
- PAM.s:
-
Protospacer-adjacent motifs
- SDSA:
-
Synthesis-dependent strand annealing
- SgRNA:
-
Single-guide RNA
- T1DM:
-
Type I diabetes mellitus
- T2DM:
-
Type II diabetes mellitus
- TALENs:
-
Transcription activator-like effector nucleases
- TNF:
-
Tumor necrosis factor
- TracrRNA:
-
Trans-activating CRISPR
- WS:
-
Wolfram syndrome
- Z.F.N.:
-
Zinc-finger nucleases
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Bora, J., Dey, A., Lyngdoh, A.R. et al. A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3459–3481 (2023). https://doi.org/10.1007/s00210-023-02631-1
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DOI: https://doi.org/10.1007/s00210-023-02631-1