Browsing by Subject "Oligonucleotide"

Now showing 1 - 4 of 4

Open Access
Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres
(American Chemical Society, 2016-04) Mumcuoglu, D.; S. Ekiz, M.; Gunay, G.; Tekinay, T.; Tekinay, A. B.; Güler, Mustafa O.
Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.
Open Access
The effect of telomerase template antagonist GRN163L on Bone-Marrow-Derived rat mMesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6
(Springer Science+Business Media, 2010) Tokcaer-Keskin, Z.; Dikmen, Z. G.; Ayaloglu-Butun, F.; Gultekin, S.; Gryaznov, S. M.; Akcali, K. C.
Telomerase activity is essential for the continued growth and survival of malignant cells, therefore inhibition of this activity presents an attractive target for anti-cancer therapy. The telomerase inhibitor GRN163L, was shown to inhibit the growth of cancer cells both in vitro and in vivo. Mesenchymal stem cells (MSCs) also show telomerase activity in maintaining their self-renewal; therefore the effects of telomerase inhibitors on MSCs may be an issue of concern. MSCs are multipotent cells and are important for the homeostasis of the organism. In this study, we sought to demonstrate in vitro effects of GRN163L on rat MSCs. When MSCs were treated with 1 μM GRN163L, their phenotype changed from spindle-shaped cells to rounded ones and detached from the plate surface, similar to cancer cells. Quantitative-RT-PCR and immunoblotting results revealed that GRN163L holds MSCs at the G1 state of the cell cycle, with a drastic decrease in mRNA and protein levels of cyclin D1 and its cdk counterparts, cdk4 and cdk6. This effect was not observed when MSCs were treated with a mismatch control oligonucleotide. One week after GRN163L was removed, mRNA and protein expressions of the genes, as well as the phenotype of MSCs returned to those of untreated cells. Therefore, we concluded that GRN163L does not interfere with the self-renewal and differentiation of MSCs under short term in vitro culture conditions. Our study provides additional support for treating cancers by administrating GRN163L without depleting the body's stem cell pools. © 2010 Springer Science+Business Media, LLC.
Open Access
Oligonucleotide-based label-free detection with optical microresonators: strategies and challenges
(Royal Society of Chemistry, 2016) Toren, P.; Ozgur E.; Bayındır, Mehmet
This review targets diversified oligonucleotide-based biodetection techniques, focusing on the use of microresonators of whispering gallery mode (WGM) type as optical biosensors mostly integrated with lab-on-a-chip systems. On-chip and microfluidics combined devices along with optical microresonators provide rapid, robust, reproducible and multiplexed biodetection abilities in considerably small volumes. We present a detailed overview of the studies conducted so far, including biodetection of various oligonucleotide biomarkers as well as deoxyribonucleic acids (DNAs), ribonucleic acids (RNAs) and proteins. We particularly advert to chemical surface modifications for specific and selective biosensing.
Open Access
Structure, mechanism and therapeutic utility of immunosuppressive oligonucleotides
(Academic Press, 2016) Bayik D.; Gursel, I.; Klinman, D. M.
Synthetic oligodeoxynucleotides that can down-regulate cellular elements of the immune system have been developed and are being widely studied in preclinical models. These agents vary in sequence, mechanism of action, and cellular target(s) but share the ability to suppress a plethora of inflammatory responses. This work reviews the types of immunosuppressive oligodeoxynucleotide (Sup ODN) and compares their therapeutic activity against diseases characterized by pathologic levels of immune stimulation ranging from autoimmunity to septic shock to cancer (see graphical abstract). The mechanism(s) underlying the efficacy of Sup ODN and the influence size, sequence and nucleotide backbone on function are considered. © Published by Elsevier Ltd.