ESR Project 4
Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge (Stockholm), Sweden
Toward improved oligonucleotides therapies. Design, synthesis and biological evaluation of new oligonucleotides based conjugates
Ass. Prof. Rula Zain
Dr. Malgorzata Honcharenko
Prof. Samir EL Andaloussi
Eliza Filipiak obtained her Master’s degree in chemistry at Adam Mickiewicz University in Poznan (Poland) in 2022.
During her Bachelor’s study she performed an internship in Institute of Bioorganic Chemistry Polish Academy of Science (Poznan) in the Department of Chemistry of Nucleic Acid Components, in which she worked with nucleic acids and she synthetized nucleotides with various backbone modifications. During her research for Master’s thesis, she also worked in the same group under the supervision of Dr. Justyna Golebiewska and she synthetized new nucleotide analogues – borane phosphonates and she tried to find new synthetic ways using H-phosphonates approach. To confirm structures, she used 1H, 13C, 31P, 11B NMR and HR-MS spectroscopy.
After graduation she started internship in Prof. Roger Strömberg’s group in Karolinska Institute in Stockholm, Sweden. The project aimed to conjugate various peptides with oligonucleotides using click chemistry in order to develop new therapeutics.
The project involves methodology development and synthesis of ON nanoconstructs for therapeutics; ONs conjugated to multiple entities for increased efficacy of ON therapy, including entities for increased tissue specificity and cell uptake, especially oligonucleotides therapy. The methodology work will also involve use and development of enzymes for synthesis of building blocks, in collaboration with Cambridge University. ON constructs for that affect the RNA levels (activation of transcription or translation), splice switching or RNA or strand invasion of DNA will be evaluated in collaboration with AstraZeneca, SOTON and SLL.
This project is carried out in strong collaboration with the following groups:
Prof. Florian Hollfelder, Cambridge University, UK
Dr. Shalini Andersson, AstraZeneca, Gothenburg, Sweden
Project summary in 3 min
The group designs and makes bioactive molecules (as well as developing synthesis methods to achieve these) in order to provide tools for biomedical problems or to explore concepts for disease therapeutics. This includes work on artificial nucleases, modified and/or conjugated biomolecules (primarily peptides and oligonucleotides) as well as ligands for specific biopolymers. The group has all equipment and localities needed for the described project. This includes fully equipped organic synthesis and biopolymer synthesis laboratory including DNA/RNA synthesizer, Peptide/PNA synthesizer, UV-Vis, CD and Fluorescence spectrometers, HPLCs, NMR-spectrometer, ESI-TOF Mass spectrometer as well as access to modelling and simulation equipment as well as software and confocal microscopy.
Dept. Of Biosciences and Nutrition NEO