Seminarium Zakładu Biofizyki

mRNA-based therapy aims to deliver precise genetic information to patient’s cells to prevent or treat specific diseases. Effective therapy depends on a variety of factors such as the encoded protein functions, mRNA translation potency and stability.Optimizing the translational potency and stability of in vitro transcribed (IVT) mRNA is crucial for increasing protein levels. IVT mRNA mimics eukaryotic mRNA, comprising a 5‘ cap, untranslated regions (UTRs), coding region and a 3‘ poly(A) tail. Modification of each structural element of mRNA can change its properties. The 5‘ cap is essential for mRNA stability, translation initiation and immune recognition. Modifications to its structure are investigated to enhance translation efficiency and reduce immunogenicity. This study focuses on synthesizing modified 5‘-cap structures incorporating pseudouridine (Ψ) and its derivatives, along with modifications of guanosine at the N1 and N2 position as a first transcribed nucleotide. Although these modifications show promise in reducingimmunogenicity within the mRNA body, their effect within cap structure remains largely unexplored. By exploring these modifications, this research aims to optimize mRNA-base therapies for enhanced efficacy and reduced immunogenic response.

Short Bio
Hai obtained his bachelor’s degree at the University of Ostrava in Czech Republic where the study course is focused on biochemical and analytical chemistry. During his bachelor study, he got interested in drug design thus he applied for master study in medicinal chemistry at Charles University in Prague, where he worked on the project synthesis of modified nucleosides in the group of Prof. Michal Hocek at the Institute of Organic chemistry and Biochemistry of CAS. After graduation he worked in the Service Technology Laboratory in the Institute of Biotechnology of CAS. Afterwards he decided to pursue his studies with a PhD, so he applied to the Jemielity group in Warsaw under supervision of dr Joanna Kowalska.