Available Technologies

Background

Inflammatory diseases affect a vast global population and drive chronic conditions like atherosclerosis and MASH. Macrophage-driven inflammation plays a key role in plaque formation and liver fibrosis, yet current treatments are limited, highlighting the need for new molecular approaches targeting this pathway.

Description and Advantages

Researchers at Kyoto University and Osaka University, working collaboratively, identified a long non-coding RNA (lncRNA) whose expression in human macrophages changes in response to cholesterol. They developed a synthetic nucleic acid that suppresses this lncRNA. When introduced into human macrophages, it inhibits the maturation of inflammatory cytokine mRNAs, reducing the expression of cytokines such as IL-6 and TNF. This work highlights a novel therapeutic target and a promising nucleic acid-based approach.

 

⮚Reduced atherosclerotic lesions and fibrotic areas in MASH liver confirmed

     Deleting the homologous lncRNA in mice suppressed macrophage-driven inflammation and slowed progression of atherosclerosis and MASH (Fig. 1). Treatment with the synthetic nucleic acid also improved inflammatory markers and liver function.

 

⮚Compatible with existing therapies

     This new approach targets macrophages to regulate inflammation via a mechanism distinct from conventional lipid- or glucose-focused therapies. It can be combined with existing treatments and may extend to inflammatory diseases beyond atherosclerosis and MASH.

Fig. 1: Suppressive effects on disease lesions caused by lncRNA deficiency

 

A: Atherosclerosis model mice (ApoE-deficient mice):
In lncRNA knockout (KO) mice, the amount of plaque stained with Sudan IV was reduced compared with lncRNA wild-type (WT) mice.

 

B&C: MASH/NASH disease model mice (GAN diet):
In lncRNA knockout (KO) mice, a reduction in the fibrosis area of the liver was observed.