江苏大学发表最新Cell子刊论文

Core Viewpoint - The increasing prevalence of metabolic dysfunction-related fatty liver disease (MASH) necessitates the development of new therapeutic strategies, as current treatment options are limited and the patient population is growing rapidly [2][5]. Group 1: MASH Overview - Approximately 100 million people globally are currently affected by MASH, with projections indicating this number could rise to 357 million by 2030 [2]. - MASH is a critical factor in the progression of liver cirrhosis and hepatocellular carcinoma, and it is a leading cause of liver transplants [2]. Group 2: Research Findings - A new strategy for large-scale acquisition of artificial cell-derived vesicles (ACDV) has been proposed, which allows for the safe and stable oral delivery of RNA drugs targeting the liver [3]. - The study demonstrated that LIMA1 siRNA (siLIMA1) delivered via the modified ACDV effectively inhibited LIMA1 protein expression in the liver, thereby preventing MASH progression and improving liver function [3][11]. Group 3: Mechanism of Action - The development of drugs targeting metabolism, inflammation, and fibrosis is crucial, as excessive accumulation of fats and other metabolic substrates leads to chronic inflammation and liver cell damage [5]. - LIMA1 gene silencing is identified as a promising therapeutic approach for MASH, given its upregulation in lipotoxic liver cells and its role in liver fibrosis associated with metabolic dysfunction [5][6]. Group 4: Delivery System - The study highlights the potential of red blood cell (RBC)-derived extracellular vesicles (RBC-EV) as a non-immunogenic delivery option for RNA drugs, although challenges remain in large-scale production and half-life limitations [7]. - A feasible strategy involves generating ACDV by squeezing red blood cells, which can then be modified with DSPE-PEG and cholic acid to enhance structural integrity and liver-targeting capabilities [8][9]. Group 5: Conclusion - The research indicates that ACDV can be easily obtained and modified to achieve oral liver-targeting capabilities, with the delivery of LIMA1-siRNA showing significant therapeutic effects against MASH [13].