Question

It was believed that mRNA technology holds significant advantages in safety and “druggability” than adenovirus therapy which uses DNA. Why? Please list at least three reasons.

Answer 1

mRNA Gene expression from messenger RNA (mRNA) represents an attractive alternative to DNA vectors, particularly for therapeutic applications. Pioneering studies of mRNA expression were conducted from the 1970s via microinjection. Following that, mRNA was transfected into mammalian cells using the cationic polymer DEAE-dextran and with cationic lipid complexes, the latter of which became the standard. Transfection via electroporation was also shown in a number of common cell lines.

Expression from mRNA has a number of advantages over DNA vectors. First, there is no risk of the genomic integration that occasionally occurs with DNA. Second, mRNA expression is based upon interaction with ribosomes located in the cytoplasm, not needing to cross the nuclear envelope as DNA does. Third, the expression is dose-dependent and rapid, occurring within minutes. Fourth, subcellular control of mRNA delivery can lead to local expression when desired. Fifth, mRNA can be less toxic and immunogenic than DNA vectors in sensitive cells, making it a preferred option for certain primary cell types. In particular, these features make mRNA a strong candidate for potential therapeutic applications. Antigen presentation arising from ex vivo mRNA transfection has been deployed in dendritic cells and T cells as a strategy for cancer immunotherapy purposes. In this context, electroporation of mRNA has become a preferred option for therapeutic cell types that are difficult to transfect with cationic lipids, such as dendritic cells