| Autor: |
Jain R; 1 Department of Molecular Biology, Moderna Therapeutics , Cambridge, Massachusetts., Frederick JP; 2 Department of Oncology, Moderna Therapeutics , Cambridge, Massachusetts., Huang EY; 3 New Venture Labs , Moderna Therapeutics, Cambridge, Massachusetts., Burke KE; 4 Non-Clinical Sciences , Moderna Therapeutics, Cambridge, Massachusetts., Mauger DM; 5 Computational Sciences , Moderna Therapeutics, Cambridge, Massachusetts., Andrianova EA; 1 Department of Molecular Biology, Moderna Therapeutics , Cambridge, Massachusetts., Farlow SJ; 2 Department of Oncology, Moderna Therapeutics , Cambridge, Massachusetts., Siddiqui S; 6 Rare Diseases , Moderna Therapeutics, Cambridge, Massachusetts., Pimentel J; 6 Rare Diseases , Moderna Therapeutics, Cambridge, Massachusetts., Cheung-Ong K; 2 Department of Oncology, Moderna Therapeutics , Cambridge, Massachusetts., McKinney KM; 3 New Venture Labs , Moderna Therapeutics, Cambridge, Massachusetts., Köhrer C; 1 Department of Molecular Biology, Moderna Therapeutics , Cambridge, Massachusetts., Moore MJ; 1 Department of Molecular Biology, Moderna Therapeutics , Cambridge, Massachusetts., Chakraborty T; 1 Department of Molecular Biology, Moderna Therapeutics , Cambridge, Massachusetts. |
| Abstrakt: |
The advent of therapeutic mRNAs significantly increases the possibilities of protein-based biologics beyond those that can be synthesized by recombinant technologies (eg, monoclonal antibodies, extracellular enzymes, and cytokines). In addition to their application in the areas of vaccine development, immune-oncology, and protein replacement therapies, one exciting possibility is to use therapeutic mRNAs to program undesired, diseased cells to synthesize a toxic intracellular protein, causing cells to self-destruct. For this approach to work, however, methods are needed to limit toxic protein expression to the intended cell type. Here, we show that inclusion of microRNA target sites in therapeutic mRNAs encoding apoptotic proteins, Caspase or PUMA, can prevent their expression in healthy hepatocytes while triggering apoptosis in hepatocellular carcinoma cells. |
