Helerin Margus “Characterization of cell-penetrating peptide/nucleic acid nanocomplexes and their cell-entry mechanisms” | University of Tartu

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Contacts of UT units

Faculty of Arts and Humanities
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Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
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    Jakobi 2, rooms 116–121, 51005 Tartu
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  • Institute of Estonian and General Linguistics
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  • Institute of Philosophy and Semiotics
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  • Institute of Cultural Research
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  • School of Theology and Religious Studies
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    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
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  • Viljandi Culture Academy
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    +372 435 5232
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    Posti 1, 71004 Viljandi
Faculty of Social Sciences
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Lossi 36, 51003 Tartu
  • Dean's Office
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  • Institute of Education
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  • Johan Skytte Institute of Political Studies
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  • School of Economics and Business Administration
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  • Institute of Biomedicine and Translational Medicine
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Vanemuise 46–208, 51014 Tartu
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  • Estonian Marine Institute
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  • Institute of Physics
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    W. Struve 1, 50091 Tartu
  • Youth Academy
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    Uppsala 10, 51003 Tartu
  • Institute of Genomics
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    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
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    +372 737 5674
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    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
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    Vanemuise 46, 51003 Tartu
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    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
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  • Estates Office
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    Ülikooli 18a, 51005 Tartu
  • Finance Office
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  • Grant Office
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    Raekoja plats 9, 51004 Tartu
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  • University of Tartu Press
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Helerin Margus “Characterization of cell-penetrating peptide/nucleic acid nanocomplexes and their cell-entry mechanisms”

Date: 
15.06.2016 - 10:15

On 15 June at 10.15 Helerin Margus will defend her doctoral thesis titled “Characterization of cell-penetrating peptide/nucleic acid nanocomplexes and their cell-entry mechanisms”.

Supervisors: TÜ MRI keemilise bioloogia professor Margus Pooga ja arengubioloogia teadur Kärt Padari.

Opponent: professor Ines Neundorf, Biokeemia Instituut, Keemia teaduskond, Kölni Ülikool, Saksamaa.

Lühikokkuvõte: Nucleic acids are highly promising candidates for the treatment of various diseases. In order to achieve biological functionality, nucleic acids need to be internalized by cells and reach their action site in cytoplasm or nucleus. However, due to the large size and negative charge, naked nucleic acids are not capable of traversing the plasma membrane of cells. A wide variety of delivery vectors have been designed to facilitate the cellular uptake of nucleic acids. One class of such vectors are cell-penetrating peptides (CPPs), short sequences of 5-40 amino acid residues, which are capable of gaining access to the interior of cells, and importantly, mediate the internalization of coupled cargo molecules.

The simplest way to couple CPPs to nucleic acids is to mix the peptide and cargo. The co-incubation of CPPs and nucleic acids leads to the formation of nanocomplexes due to electrostatic and hydrophobic interactions between the peptide and cargo. Co-incubation strategy has been shown to yield high bioactivities of cargos in numerous studies. However, this approach has not reached clinical trials yet. One reason behind this is the complicated physicochemical characterization of the forming nanocomplexes. However, in order to be considered for implementation in biomedicine the properties of CPP/nucleic acid complexes such as size, morphology and charge need to be characterized in detail. Another bottleneck which impedes the implementation of non-covalent strategy for nucleic acid delivery is the poor knowledge of the cellular uptake mechanisms and intracellular trafficking of CPP/nucleic acid nanocomplexes. However, detailed characterization of the cell internalization pathways and cellular trafficking of CPP/cargo complexes are essential for avoiding undesired side effects and refining their properties in order to yield higher activities of delivered cargo.

The main objectives of the current thesis were to characterize the physicochemical properties of CPP/nucleic acids nanocomplexes formed by PepFect and NickFect type carrier peptides, and to examine the cellular uptake mechanisms and intracellular trafficking of nanocomplexes and nucleic acids.

Location: 
Riia 23b, room 105
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