5.2. PCI for the Delivery of mRNA
The use of mRNA for therapeutic and vaccination approaches has a very great potential [176]. Although the incorporation of modified bases into mRNA molecules have reduced the susceptibility for mRNA inactivation by RNases [177], mRNA stability is still an issue, and the lack of efficient and specific methods for in vivo delivery of mRNA molecules is still a major barrier for the realization of their therapeutic potential. Most mRNA delivery methods depend on endocytic uptake, and, given the instability of mRNA, it is very important to be able to release the mRNA molecules from endocytic vesicles before they are degraded [178]. PCI is an ideal technology for achieving this, since endosomal release can be induced instantly by illumination shortly after mRNA uptake. The first study reporting PCI-mediated mRNA delivery in vitro was published by Bøe et al. [179], using PEI as a delivery vehicle for the mRNA. Later experiments by the same group showed efficient PCI-induced mRNA delivery also with a poly-l-arginine delivery vehicle. Since this vehicle has no endosomolytic properties in itself, in this case PCI could be used for turning mRNA expression on, against a background of virtually no expression without PCI. PCI-mediated mRNA delivery was also investigated with various PAMAM-based formulations, but while such formulations were effective for PCI-mediated siRNA delivery, they did not work with mRNA [167]. In vivo, PCI-mediated mRNA delivery using delivery vehicles have so far largely been unsuccessful, but very promising results have recently been obtained with PCI-mediated delivery of various types of “naked” mRNA molecules (Høgset et al., manuscript in preparation).
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