FIGON DMD

Lotte Tholen

mRNA Product Specialist, RIBOPRO

Lotte Tholen obtained her MSc in Molecular Mechanisms of Disease (2017) and her PhD in Molecular Biology from the Radboud University (2023). Inspired by the potential of mRNA to cure previously untreatable diseases she continued her career at RIBOPRO in 2022. In her role as mRNA Product specialist, she translates current and future needs of the customer into a custom mRNA product and supports customers in designing and executing their mRNA projects. She also contributes to RIBOPRO's extensive internal R&D program as part of the motivated science team. She uses her previously acquired experience in analysing big datasets to optimize mRNA design and activity to expand the potential of mRNA, especially in therapeutic use.

Presentation: Drug waste of ready-to-administer syringes in the Intensive Care Unit: aseptic syringes versus prefilled sterilized syringes

In vitro transcription (IVT) mRNA is emerging as a new class of therapeutic agents. Although structurally similar to naturally occurring mRNA, exogenous IVT mRNA, is immunostimulatory unless strategies for reducing the immune stimulation are applied. This poses a significant challenge for therapeutic applications, as immune activation inhibits protein synthesis, cellular toxicity, and pro-inflammatory cytokine release. Current deimmunizing strategies mostly rely on the use of modified nucleotides. Although proven effective for mRNA vaccines, the effects of chemically modified nucleotides are not completely understood yet and may have unintentional side effects in mRNA therapeutics. Therefore, we aimed to develop a sequence engineering strategy to improve safety and protein yield of the mRNA, thereby widening the therapeutic window of mRNA. Here we present our method based on U and/or C depletion while keeping codon usage and secondary structure in mind and show that it improves protein yield significantly. This approach is a valuable and safe alternative for the use of chemically modified nucleotides in IVT mRNA.