mRNA-Based Approaches to Treating Liver Diseases

Abstract

Diseases that affect the liver account for approximately 2 million deaths worldwide each year. The increasing prevalence of these diseases and the limited efficacy of current treatments are expected to stimulate substantial growth in the global market for therapeutics that target the liver. Currently, liver transplantation is the only curative option available for many liver diseases. Gene therapy represents a valuable approach to treatment. The liver plays a central role in a myriad of essential metabolic functions, making it an attractive organ for gene therapy; hepatocytes comprise the most relevant target. To date, viral vectors constitute the preferred approach to targeting hepatocytes with genes of therapeutic interest. Alternatively, mRNA-based therapy offers a number of comparative advantages. Clinical and preclinical studies undertaken to treat inherited metabolic diseases affecting the liver, cirrhosis and fibrosis, hepatocellular carcinoma, hepatitis B, and cytomegalovirus using lipid nanoparticle-encapsulated mRNAs that encode the therapeutic or antigenic protein of interest are discussed.

Deciphering hepatocellular carcinoma pathogenesis and therapeutics: a study on anoikis, ceRNA regulatory network and traditional Chinese medicine

“…Apart from causing illness in immunocompromised individuals, human cytomegalovirus is increasingly recognized for its involvement in tumor pathogenesis, as it has been detected in various tumor tissues such as glioblastoma and several adenocarcinomas (Pasquereau et al, 2017;Herbein, 2018;Nauclér et al, 2019). Emerging evidence suggests that human cytomegalovirus may contribute to advanced liver disease, providing valuable insights for the development of novel therapeutic approaches for HCC treatment (Cacicedo et al, 2022;Khalil et al, 2022). Cytokines, as crucial immune system mediators, interact with specific cellular receptors that are upregulated during cell activation in various diseases, particularly cancer (Scheller et al, 2021).…”

Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy

“…Stability issues, the intricacies of large-scale manufacturing, and considerable production and treatment costs can impede their wide and accessible application to all patients [ 114 ]. A promising alternative involves the in vivo production of antibodies via delivery of antibody-encoded mRNA, a method that can lead to efficient in vivo expression of desired antibodies [ 115 , 116 ].…”