Objective
The project is aimed at the development of efficient approaches to the delivery of oligomeric and long chain DNA to mammalian cells and their cell nucleus that are needed for elaboration of efficient methods of gene therapy. The tasks of the project include:
Development of new carrier structures capable of transporting DNA into mammalian cells and into cell nucleus, such as steroid derivatives, non-toxic dioxin analogs and specific peptides;
Identification by SELEX approach of the DNA sequences that can efficiently enter the cells and cell nucleus;
Investigation of the structures responsible for internalisation and nuclear targeting of pathogenic DNAs naturally capable of transfecting cells;
Investigation of cellular uptake and transport to the nucleus of oligonucleotides and DNA conjugated to the synthetic carriers and the targeting nucleotide sequences and development of efficient transfection protocols;
Application of the developed transportation methods to delivery of antisense oligonucleotides and reporter genes to different cells in culture (and to delivery of deficient cloned genes to cells).
The expected results of the project are the following. Synthetic molecules capable of efficiently entering cells and cell nucleus: non-toxic dioxin analogous, steroid derivatives and peptide-like molecules will be prepared. Natural single-stranded and double-stranded DNA sequences capable of efficiently entering cells and localise in the cell nucleus will be identified by using SELEX-like combinatorial approaches. Methods for the conjugation of these molecules and sequences to DNA and design of vector virus-like supramolecular complexes capable of delivering into cells the DNA equipped with the nucleus targeting vector molecules will be elaborated. These methods will be tested in experiments designed to inhibit proliferation of cancer cells, to overcome multidrug resistance of cancer cells, and to arrest proliferation of influenza virus in mammalian cells. The planned researches can result in the development of methodologies, which are important for practical applications in gene therapy.
Topic(s)
Call for proposal
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23538 Lübeck
Germany