Looking into the possibilities of cure of the type 2 diabetes mellitus by nanoparticle-based RNAi and CRISPR-Cas9 system: A review

Hyperglycemia is the hallmark of T2DM, related to many candidate genes, e.g., MAPK4, GCKR, STAT3, SOCS3, PTPN1 and PEPCK. To detect new variants of the susceptible genes related to T2DM, a genome-wide association study (GWAS) is being undertaken as well. The existing treatments are unable to address the root cause of the disease at the genetic level and in this regard, the concept of RNAi and most recently, the invention of CRISPR-Cas9 system holds a huge promise and paves a new direction in the treatment strategy of the disease at the genetic level, with a possibility for complete cure, although, issues like low efficiency and off-target problems have impeded their applicability. Additionally, the target-specific delivery using viral carriers also poses serious safety issues. Hence, the current scenario underscores the need for suitable nanocarriers for delivery of the above payloads to the target site and in the present narrative review, we attempt to draw the current understanding of RNAi on the T2DM treatment with the help of nanoparticle encapsulated anti-miR, siRNA, shRNA delivery, also nanoparticle-based CRISPR-Cas9 delivery, to explore the prospect of the complete cure of the disease. [Display omitted]