Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers

Abstract

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients' quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducing inflammation and pain in the joint targeting specific molecular key players, instead of a systemic and generalized approach like with non-steroidal anti-inflammatory drugs. Aptamers' properties, including structure versatility, reduced immunogenicity, and flexible administration methods, position them as high-potential candidates for OA treatment. This review summarizes results from clinical trials applying monoclonal antibodies to treat OA, preclinical research, and the development of aptamers as a new generation of targeting agents. Meanwhile, it provides a comprehensive comparison of the characteristics, advantages, and limitations of aptamers versus monoclonal antibodies. Notably, the promising applications of aptamers, demonstrated in other inflammatory and degenerative conditions, underscore their potential for OA therapy. We anticipate that the application of aptamer could offer a new way of OA pharmacological intervention.

Keywords: MT: Oligonucleotides: Therapies and Applications; monoclonal antibodies; nucleic acid aptamers; osteoarthritis; targeted therapy.

Graphical abstract

Figure 1

Schematic overview of aptamer selection via SELEX and target binding (A) Binding of aptamer to its target through conformational recognition. Through the SELEX process, an aptamer forms a unique three-dimensional (3D) structure that enables specific binding to its target, functioning as a highly selective inhibitor. (B) The essential steps of a standard SELEX technique. SELEX, systematic evolution of ligands by exponential enrichment; PCR, polymerase chain reaction; ssDNA, single-stranded DNA; dsDNA, double-stranded DNA; RNA, ribonucleic acid; DNA, deoxyribonucleic acid.

Figure 2

Clinical trials summary of monoclonal antibodies for OA treatment IL-1, interleukin-1; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; NGF, nerve growth factor; ADAMTS-5, a disintegrin and metalloproteinase with thrombospondin motifs 5.

Figure 3

Targeted treatment for OA using functionalized nanocarriers with aptamers specific to cells type To show the target therapy function of aptamer-based nanoparticles for OA, components are assembled in one nanocarrier, including imaging marker (fluorescent dyes or radioactive agents) and therapeutics (mAbs, drugs, oligonucleic acids, and chemotherapeutic agents). mAbs, monoclonal antibodies; siRNA, small interfering RNA; miRNA, microRNA; RNA, ribonucleic acid.