Treating liver cirrhosis by regulating intracellular SAM concentration through a negative feedback mechanism
Liver-protective therapy delays the progression of liver cirrhosis through mechanisms such as antioxidation, anti-inflammation, and the promotion of hepatocyte repair. S-adenosyl-L-methionine (SAM) is a common liver supplement and serves as an important adjunctive therapy.
The clinical practice has confirmed that exogenous SAM supplementation can, to some extent, delay the progression of liver disease. However, existing supplementation therapies still have significant limitations.
We aim to achieve negative feedback Regulation of intracellular SAM concentration by an RNA element.
We developed an mRNA drug that carries the MAT1A ORF encoding MATI enzyme and incorporated the SAM-responsive aptazyme in its 3' UTR. The MAT I enzyme catalyzes the synthesis of SAM.
We went through several experimental cycles in our wet experiments before fully developing ReguSAMe. Specifically, we selected ribozymes and SAM riboswitches, modified aptazymes, constructed liver cirrhosis cell models, and verified the cutting efficiency. Ultimately, we have developed an mRNA-based liver cirrhosis treatment method based on ReguSAMe.
Our dry-lab team leverages advanced computational models and custom software platforms for RNA design and analysis. From secondary structure prediction to small molecule binding and RNA-protein interaction simulations, our tools provide efficient and reliable guidance for experimental validation, accelerating the overall research process.
The achievements of HP focus on inclusivity, IHP, and collaboration.In terms of inclusivity, we have carried out various activities and written the "Inclusivity Guide." Regarding IHP, we approached from three aspects: wet lab, dry lab, and HP, to communicate with stakeholders. In the area of collaboration, we co-hosted this year's CCiC and participated in many conferences for exchange. The three aspects are advanced in parallel, jointly promoting the implementation and realization of the project.
Learn more noteworthy details about ReguSAMe from our Wiki page.
