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Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal
intensive treatments. One of the most commonly mutated proteins in GBM is epidermal growth factor receptor variant
III (EGFRvIII), which has been linked to radiation and chemotherapeutic resistance, and enhanced tumorigenic behavior. Its
inhibition can interfere with growth of GBM so a few drugs including monoclonal antibodies and tyrosine kinase inhibitors
currently are used in clinic. However, some of these drugs resulted in toxicity and acquired resistance, it?s extremely urgent to
develop novel drug targeting EGFRvIII with low toxicity and high specificity. DNA aptamers may be a good alternative solution.
After several rounds of selection with an approach named cell systematic evolution of ligands by exponential enrichment (Cell-
SELEX), aptamers specifically bound to EGFRvIII-overexpressing U87MG cells (U87Δ) were selected. A biotin-avidin ELISA
method was used to measure the binding affinity. Selected aptamers were able to distinguish the U87Δ cell line from other cell
line and with an equilibrium dissociation constant (Kd) in the nanomolar to picomolar range. One of these aptamers specifically
bound to EGFRvIII protein with high affinity as that of EGFR antibody, and could localize in the cell nucleus. In the siRNA
transfection experiment, DNA aptamer mediated siRNA delivery with the same efficiency compared with lipofectamine2000.
These cell-based aptamers are promising molecular probes for the diagnosis and treatment of GBM. Aptamers can recognize the
membrane protein of target cells and be endocytosed, so they may be effective vehicles for drugs or siRNA delivery.
Biography
Yan Tan has completed her M.D. at the age of 26 years from Southern Medical University of neurobiology and worked at Shenzhen Institutes of
Advance Technology as a research assistant.
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