KEY WORDS: thermodynamics of nucleic acids, G-quadruplexes, triplexes, oncogene transcription regulation, cell lines
Principal Investigator: Dr. Anna Pasternak, Assoc. Prof.
I. Project description
We plan to investigate for the first time various aspects of designing oligonucleotide tools named foldback triplex-forming oligonucleotides (FTFOs) targeted towards model G-quadruplex forming sequence which is pivotal regulatory element in transcription of c-Myc oncogene. The main aim of the project is focused on comprehensive physicochemical and biological characterization of novel oligonucleotide tools and investigation of their potential in selective unfolding of G-quadruplex structure as well as in repression of oncogene regulatory element which is pivotal for tumor survival. In general, the project will be focused on two main points: (i) development of FTFOs that are optimal for selective and specific unfolding of particular G-quadruplex structure, (ii) investigation of therapeutic potential of novel tools in vitro and in cell cultures. The project will answer on how to design novel oligonucleotide tools which can efficiently and selectively unfold G-quadruplex structures and arrest biological role of this kind of triggers. The systematic investigation presented herein, as the basic studies, could facilitate designing of FTFO-based drugs with promising anticancer properties in the future.
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