Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is one of the most common chronic liver diseases worldwide. Closely linked to diabetes and obesity, its global prevalence ranges from 15% to 40%. Although the U.S. FDA recently approved Rezdiffra, the first treatment for MASLD, its efficacy rate is only 25%, and it carries a risk of hepatotoxicity.
A research team led by Assistant Professor Wang Chih-Hao from China Medical University has developed an innovative gene-editing technology called the CRISPR Multiplexed Activation Platform (CRISPR-MAP). This platform can simultaneously activate multiple genes, enhancing the therapeutic potential of stem cells. CRISPR-MAP can deliver up to 20 guide RNAs in a single plasmid and activate transcription of multiple genes in one delivery. As a result, mesenchymal stem cells (MSCs) can secrete a greater number of therapeutic factors and precisely target specific tissues. Compared to traditional gene-editing methods, CRISPR-MAP not only improves the biological activity of stem cells but also reduces the complexity of cell engineering, ensuring consistency in product quality.
Revolutionizing Multi-Gene Activation and Cell Therapy: A New Solution for Metabolic Diseases
Using CRISPR-MAP, the team transformed MSCs into brown adipose tissue-like mesenchymal stem cells, referred to as BATmen. The core advantage of the BATmen therapy lies in its multi-gene activation mechanism. Through the CRISPR-SAM system, key genes such as PPARγ, PGC1α, and UCP1 are simultaneously activated, promoting the differentiation of MSCs into brown adipocytes. This improves the metabolic microenvironment of the liver. Compared with conventional single-gene therapies, CRISPR-MAP offers a more comprehensive regulatory strategy, enhancing energy expenditure while reducing fat accumulation and inflammation. Additionally, this technology utilizes a non-viral transposon system for gene delivery, greatly enhancing safety and minimizing potential side effects.
In animal studies, BATmen demonstrated successful liver targeting and significantly improved metabolic function in mice. In a high-fat diet-induced MASLD mouse model, four rounds of BATmen cell therapy effectively reduced liver fat accumulation, increased basal metabolic rate, and significantly improved glycemic stability. These findings not only confirm the potential of BATmen for MASLD treatment but also open new avenues for applying cell therapy to metabolic diseases.
Industry Development and Future Prospects: Ushering in a New Era of Cell Therapy
Assistant Professor Wang Chih-Hao stated that CRISPR-MAP represents a major breakthrough in stem cell therapy, offering new hope for patients with MASLD and diabetes. The team aims to develop BATmen into a safe, effective, and scalable cell therapy to fill the gap in current treatment options. To accelerate commercialization, they have filed multiple patents in Taiwan, the U.S., China, and Japan. They have also partnered with Ever Supreme Bio Technology to develop large-scale clinical-grade MSC production techniques, laying the groundwork for future cell therapy markets.
Currently, the CRISPR Multiplexed Activation Platform is advancing toward clinical trials. The team plans to further promote clinical studies and seek international partners for joint development. Beyond MASLD, this technology has potential applications in other metabolic diseases and even neurodegenerative disorders. As cell therapies continue to evolve, BATmen are expected to become a standard treatment for metabolic diseases, offering new health solutions to millions of patients worldwide.
Resource: 改造細胞活化基因 精準靶向肝臟提高代謝減少脂肪蓄積
