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dc.contributor.advisorGürsel, İhsan
dc.contributor.authorDereli, İhsan
dc.date.accessioned2016-01-08T18:25:48Z
dc.date.available2016-01-08T18:25:48Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/11693/15868
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Graduate School Engineering and Science of Bilkent University, 2013.en_US
dc.descriptionThesis (Master's) -- Bilkent University, 2013.en_US
dc.descriptionIncludes bibliographical references leaves 71-86.en_US
dc.description.abstractCpG ODNs are potent immunotherapeutic agents. In human, two major classes of CpG ODNs were shown to induce differential immune activation. D ODNs are strong IFNα inducers, thus promising antiviral agents, whereas K ODNs are effective against bacterial infections. However, their effects cannot be combined. When K and D type ODNs are used simultaneously, K ODN cancels D specific effect, a phenomenon known as K and D ODN dichotomy. The prime reason for this counter acting K ODN action was subcellular compartmentalization of K type CpG ODNs upon internalization. Besides, CpG ODNs have labile nature. When investigated in clinical trials, these nucleic acid based ligands are eliminated upon administration and displayed limited bio-availability due to nuclease digestion. Hence, efforts to protect in vivo performance, and increase stability and accumulation near target cells became a crucial task. Liposome technology offers a simple and mild approach to harbor these ODNs within membrane bilayers and protect them. We also reasoned that, if we use liposomes that alter subcellular fate of K and D ODNs, we can retain both K and D effect when liposomal ODNs are co-administered and the breadth of immunotherapeutic spectrum could be improved. This thesis was designed to understand and characterize different types of CpG ODNs loaded into different liposomes and aimed to determine their activities in different in vitro and in vivo settings. Our results revealed that when two different classes of clinically important CpG ODNs were encapsulated within proper liposome types, it is possible to recapitulate both K and D type ODN effect in PBMCs. Furthermore, in a vaccine model against H. felis, although initially did not induce significantly higher anti H.felis immunity, liposomal CpG ODNs improved persisting antibody levels for extended periods compared to free counterparts. Collectively, our results demonstrate that this platform allows more effective in vivo utilization of CpG ODNs and can be formulated to develop more efficient means to combat several health problems, ranging from cancer to allergy.en_US
dc.description.statementofresponsibilityDereli, İhsanen_US
dc.format.extentxvi, 105 leaves, graphics, tablesen_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectLiposomeen_US
dc.subjectCpG ODNsen_US
dc.subjectHelicobacteren_US
dc.subjectVaccineen_US
dc.subjectD and K dichotomyen_US
dc.subject.lccQR185.2 .D47 2013en_US
dc.subject.lcshNatural immunity.en_US
dc.subject.lcshImmunity, Natural--Physiology.en_US
dc.subject.lcshLiposomes.en_US
dc.subject.lcshImmunological adjuvants.en_US
dc.subject.lcshImmunotherapy.en_US
dc.subject.lcshCell immunity.en_US
dc.titleInvestigation of improved immunostimulatory activity of D and K type CpG ODNs in liposomesen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreeM.S.en_US


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