‘miRNA shows higher delivery efficiency to chondrocytes for treating osteoarthritis’

A research team at Seoul National University said ribonucleic acid therapy (RNA) showed higher delivery efficiency to chondrocytes in cartilage compared to conventional antisense oligonucleotide in treating osteoarthritis (OA).

Professor Kim Jin-hong of the Department of Biological Sciences at Seoul National University makes a presentation in an online global meeting hosted by the Center for RNA Research at the Institute for Basic Science (IBS) and Seoul National University on Wednesday.

The research team, led by Professor Kim Jin-hong of the university’s Biological Sciences Department, has designed the study using anti-mir-155 antisense oligonucleotide (ASO) with the phosphorothioate (PS) backbone modification and a mix of DNA and locked nucleic acid and to develop micro RNA (miRNA) targeting therapy for OA.

Professor Kim made the presentation in an online global meeting hosted by the Center for RNA Research at the Institute for Basic Science (IBS) and Seoul National University on Wednesday for sharing the latest knowledge and development of RNA therapeutics, where well-known professors worldwide have joined to present their interim study results.

Professor Kim said that the accumulation of reactive oxygen species accelerates OA development through oxidative stress that causes chondrocytes to age and permanently stops dividing. He added that the mainstream researches of OA have been focusing on identifying signaling pathways or factors regulated by inflammatory cytokines.

However, therapeutic targeting of the tumor necrosis factor-alpha (TNF-a) and interleukin 1 beta (IL-1b) has been less successful in treating OA than rheumatoid arthritis.

According to Kim, the main advantage of RNA therapies is that cartilage has very thick and dense layers of the matrix where big molecules like antibodies are hard to penetrate.

In contrast, a small-sized oligonucleotide with flexibility is easier to target the chondrocyte embedded in the cartilage layers.

As a target of the oligonucleotide-based therapy, the research team looked for abundantly expressed candidates and specifically regulated in the OA cartilage. They found that mir-155 met the criteria.

In the study, mir-155 was substantially upregulated in the human cartilage, and their targets were negatively enriched transcriptome of the cartilage and the aged cartilage.

Osteoarthritis is a degenerative disease present in 30 percent of men and women over 65, occurring in all joints of humans. It is the most common type of arthritis and is primarily characterized by cartilage destruction. Its main symptoms include pain, stiffness, swelling, bony enlargement of joints, and reduced movement.

“We plan to test this therapeutic efficacy in a preclinical animal model, and our lab is trying to accomplish therapeutic targeting of the miRNA for treating OA,” Kim said.

Kim and his colleagues have been working to find the molecular mechanisms underlying musculoskeletal diseases and developing therapeutic strategies against related diseases.