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The study of physico-chemical properties of dsDNA and siRNA complexes with the new transfection carriers

Weronika Andrzejewska

Abstract

One of the current challenges facing medicine is the prospect of effective treatment of a wide spectrum of previously incurable diseases. The solution seems to be gene therapy developed over the last decades, consisting in the treatment of genetic diseases with the use of therapeutic fragments of nucleic acids (e.g. siRNA). Despite well-established theoretical assumptions and a number of successfully conducted tests, the free and unlimited use of gene therapy for therapeutic purposes is still a huge challenge. Successfully bypassing the immune response mechanisms of the patient's target cells is very difficult. In view of these facts, an important problem turns out to be a successful transfection process, i.e. introducing the therapeutic material inside the target cells. An interesting group of chemical compounds showing the desired properties are oligomeric cationic surfactants. In this dissertation, two series of dicationic surfactants and two tricationic surfactants were tested as transfection agents. Based on the research, it was found that all these surfactants permanently complex dsDNA and siRNA oligomers to form their stable lipoplexes, and this process is most efficient with the use of surfactants from the group of ammonium dichlorides. The obtained results are very promising and predispose the tested oligomeric surfactants for further research on their potential application in gene therapy.
Record ID
UAM530027e288ab4291970d75c9906f43d4
Diploma type
Doctor of Philosophy
Author
Title in Polish
Badania właściwości fizyko-chemicznych kompleksów dsDNA i siRNA z nowymi czynnikami transfekcyjnymi
Title in English
The study of physico-chemical properties of dsDNA and siRNA complexes with the new transfection carriers
Language
  • pol (pl) Polish
  • eng (en) English
Certifying Unit
Wydział Fizyki [nowa struktura organizacyjna] (SNŚ/WyF)
Scientific discipline (2.0)
6.6 physical sciences
Year of creation
2021
Start date
2018
Defense Date
02-02-2021
Title date
02-02-2021
Supervisor
URL
https://hdl.handle.net/10593/26035 Opening in a new tab
Keywords in English
gene therapy; surfactants; circular dichroism spectroscopy; small angle X-ray scattering
Abstract in English
One of the current challenges facing medicine is the prospect of effective treatment of a wide spectrum of previously incurable diseases. The solution seems to be gene therapy developed over the last decades, consisting in the treatment of genetic diseases with the use of therapeutic fragments of nucleic acids (e.g. siRNA). Despite well-established theoretical assumptions and a number of successfully conducted tests, the free and unlimited use of gene therapy for therapeutic purposes is still a huge challenge. Successfully bypassing the immune response mechanisms of the patient's target cells is very difficult. In view of these facts, an important problem turns out to be a successful transfection process, i.e. introducing the therapeutic material inside the target cells. An interesting group of chemical compounds showing the desired properties are oligomeric cationic surfactants. In this dissertation, two series of dicationic surfactants and two tricationic surfactants were tested as transfection agents. Based on the research, it was found that all these surfactants permanently complex dsDNA and siRNA oligomers to form their stable lipoplexes, and this process is most efficient with the use of surfactants from the group of ammonium dichlorides. The obtained results are very promising and predispose the tested oligomeric surfactants for further research on their potential application in gene therapy.

Uniform Resource Identifier
https://researchportal.amu.edu.pl/info/phd/UAM530027e288ab4291970d75c9906f43d4/
URN
urn:amu-prod:UAM530027e288ab4291970d75c9906f43d4

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