Title:mRNA as a Versatile Tool for Exogenous Protein Expression
VOLUME: 12 ISSUE: 5
Author(s):Andreas N. Kuhn, Tim Beißert, Petra Simon, Britta Vallazza, Janina Buck, Brian P. Davies, Ozlem Tureci and Ugur Sahin
Affiliation:TRON (Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131 Mainz, Germany.
Keywords:Gene therapy, genetic modifications, immunotherapy, in vitro transcription, mRNA, RNA stability, stem cells,
T-cell therapy, transfection, translation
Abstract:Several viral and non-viral vectors have been developed for exogenous protein expression in specific cells.
Conventionally, this purpose is achieved through the use of recombinant DNA. But mainly due to the risks associated with
permanent genetic alteration of cells, safety and ethical concerns have been raised for the use of DNA-based vectors in
human clinical therapy. In the last years, synthetic messenger RNA has emerged as powerful tool to deliver genetic information.
RNA vectors exhibit several advantages compared to DNA and are particularly interesting for applications that
require transient gene expression. RNA stability and translation efficiency can be increased by cis-acting structural elements
in the RNA such as the 5’-cap, the poly(A)-tail, untranslated regions and the sequence of the coding region. Here
we review recent developments in the optimization of messenger RNA as vector for modulation of protein expression emphasizing
on stability, transfection and immunogenicity. In addition, we summarize current pre-clinical and clinical studies
using RNA-based vectors for immunotherapy, T cell, stem cell as well as gene therapy.
