Gene therapy using miRNA treatment suppresses the expression of bone-forming defective genes and raises the expression of genes that become dormant during bone building

Abstract

According to recent discoveries from various metabolic disease studies, gene therapy is a fantastic opportunity to alleviate skeletal problems. By adding aspartic acid octapeptide (D8) to the AAV2 vector's VP2 capsid protein N-terminal region, Almeciga et al. created a new strategy for targeted delivery of the AAV vector to the bone in 2018. After 3 months of injection into MPS IVA rats, the AAV2-D8 vector showed a significant affinity for HA, a significant number of viral vector copies, and increased enzyme activity in bone. These findings show that the capsid vector bone-targeting peptide may be employed to retarget the AAV vector and treat bone diseases. Modified microRNA (miRNA), on the other hand, has begun treating bone disorders to push gene therapy to molecular and metabolic control levels. Sun et al. presented a 2019 study on the efficacy of miRNA-based gene therapies for bone regeneration, increasing bone structure, and preventing osteoporosis and osteoporotic fractures. MiRNAs have been identified as critical in a number of cell processes in bone cells, including proliferation and differentiation. MiRNA treatment has two effects: it suppresses the expression of bone-forming defective genes and raises the expression of genes that become dormant during bone building. However, this sort of treatment can induce low stability, limited bone specificity, and off-target effects. Recent research has demonstrated that integrating miRNAs with a vector such as AAV or a baculovirus vector has increased bone delivery specificity, addressing the specificity and efficacy restrictions of miRNA delivery. Viral Vector-based Systemic miRNA Delivery Systems is the term for these systems. The MiRNA-based treatment, which has tremendous bone treatment potential, needs additional investigation. For future gene therapy methods, we must produce clinically effective bone degradation medicines with no off-target effects. In patients with skeletal diseases causing osteoporosis, preventing and resolving bone and cartilage lesions remains an unfulfilled aim. Compared to non-targeting treatment, bone-targeted therapy offers several benefits, including delivering the right amount of medicine to skeletal lesions, reducing drug dose, minimizing side effects, and enhancing therapeutic efficacy. Bone-targeting approaches based on polymeric oligopeptides and nanoparticles have been developed in recent decades. Nevertheless, these achievements are still in the preclinical stage. To reach the clinical level, additional study is needed. Gene therapy combined with bone-targeting techniques such as acid amino acid oligopeptide and nanomedicine may be the next generation of one-time systemic bone disease therapies.