Sentetik cpg oligodeoksinükleotid/katyonik pettid komplekslerinin immün stimülan özelliklerinin belirlenmesi

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2013

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Güngör, Bilgi
Gürsel, Mayda
Gürsel, İhsan

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Yapısal olarak birbirinden farklı CpG motifleri içeren sentetikoligodeoksinükleotidler (ODN) insan immün sistem hücrelerini de farklı şekillerdeuyarmaktadır. Aşı adjuvantı/immünoterapötik ajan olarak klinik denemelere girmişolan K-tipi ODN’ler güçlü B hücre etkinleştirici ve plasmasitoid dendritik hücre(pDC) olgunlaştırıcı, TNF üretici özelliğe sahiptir. Buna karşı, D-tipi ODN’lerpDC’lerden yüksek miktarda IFN üretimine yol açmaktadırlar. Bu aktivite, DODN’lerin G-quadruplex temelli nanometre ebatında parçacıklar oluşturabilmeözelliğine dayalıdır ve bu sebeple üretimlerinde yaşanan sorunlar bu ODN tipininklinik denemelere ulaşmasını engellemektedir. D-ODN aktivitesini tekrarlayabilenve klinik gelişime müsait yeni ajanlar oluşturabilmek amacıyla bu projede K-tipiODN’leri katyonik peptitlerle kompleksleyip kararlı nanoyapılar oluşturmayıhedefledik. Bu projede esnek olmayan ikincil yapıya sahip kısa bir CpG ODNsekansının HIV virüsünden köken alan katyonik Tat peptidi(47-57) ilekomplekslendiğinde nükleazlara dirençli nanohalkalar oluşturduğugösterilmektedir. Nanohalkaların hücre içine alımı arttırdığı ve ODN’i erkenendozomlara hedefleyerek pDC’lerden yüksek miktarda IFN salımına yol açtığıbulunmuştur. Konvansiyonel K tipi ODN’lerle karşılaştırıldığında nanohalkalarınŞap aşısına karşı Th1 ağırlıklı immün yanıt oluşturdukları ve terapötik tümör aşısıadjuvantı olarak Ovalbümin (OVA) proteini ifade eden EG.7 timoma tümörütaşıyan C57BL/6 farelerde daha üstün anti-tümör immünite tetiklediklerigösterilmektedir. Bu sonuçlar, nanohalkaların D-ODN aktivitesini tekrarlayabilenyeni ajanlar olarak klinik uygulamalarda yerini alabileceğine işaret etmektedir.Anahtar kelimeler: TLR9, CpG oligodeoksinükleotidler, katyonik peptidler,ODN-peptid nanoparçacıkları, aşı adjuvantı, anti-kanser ajan

Subject Keywords

Malzeme Bilimleri, Özellik ve Test, TLR9, CpG oligodeoxynucleotides, Cationic peptides, ODNpeptide nanoparticles, Vaccine adjuvant, Anti-cancer agent

URI

https://app.trdizin.gov.tr/publication/project/detail/TVRNd05qWTI
https://hdl.handle.net/11511/49845

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Department of Biology, Project and Design

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Citation Formats

B. Güngör, M. Gürsel, and İ. Gürsel, “Sentetik cpg oligodeoksinükleotid/katyonik pettid komplekslerinin immün stimülan özelliklerinin belirlenmesi,” 2013. Accessed: 00, 2020. [Online]. Available: https://app.trdizin.gov.tr/publication/project/detail/TVRNd05qWTI.