Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

A Network Biology Approach to Understanding the Tissue-Specific Roles of Non-Coding RNAs in Arthritis

“…Additionally, we demonstrate that as ceRNAs, lncRNAs and circRNAs can regulate one or more miRNAs, suggesting that miRNAs are important coordinating signals and therefore potential therapeutic targets ( 44 ). Targeting non-coding RNAs with antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to selectively modulate their expression in specific tissue types could have therapeutic benefit for OA and RA ( 45 ).…”

Polymeric Hydrogels for Controlled Drug Delivery to Treat Arthritis

“…Oligonucleotide-based therapeutics for arthritis have shown remarkable progress over the last few years with the potential to inhibit the synthesis of specific proteins within cells such as chondrocytes, fibroblasts, and osteocytes and further lower the levels of inflammatory cytokines or catabolic enzymes in blood or synovial fluid [ 137 , 138 ]. However, ASO-based therapeutics face challenges in crossing the formidable biological barrier of articular cartilage because of their size and anionic charge.…”

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

“…Thus oligonucleotide therapy in bone may have greater applications where delivery need only be localized, such as with bone healing or orthopedic injury, (45 ) or for intra‐articular injection for osteoarthritis. ( 46 )…”

“…Thus oligonucleotide therapy in bone may have greater applications where delivery need only be localized, such as with bone healing or orthopedic injury, (45) or for intra-articular injection for osteoarthritis. (46) Morpholinos are nonionic oligodeoxynucleotide analogs that can bind in an antisense manner to block translation, splicing, or even miRNAs and their targets. Custom morpholinos have emerged as formidable drugs for treating specific genetic disorders where exon skipping is a viable option.…”