RNA-based aptamers as high affinity ligands for tumor cell surface epitopes"
Esposito, Carla Lucia (2009) RNA-based aptamers as high affinity ligands for tumor cell surface epitopes". [Tesi di dottorato] (Inedito)
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Structured single-stranded nucleic acids, or aptamers, bind target molecules ranging from small chemical compounds to cells and tissues with high affinity and specificity. Thanks to their unique characteristics (low size, good affinity for the target, no immunogenicity, chemical structures that can be easily modified to improve their in vivo applications), aptamers are perfectly suitable to different areas of biotechnology. Currently, several aptamers are in the clinical pipeline for applications and their functional repertoire has expanded with aptamers as reagents for the targeted delivery. Here we demonstrate that aptamers are efficient tools to bind/inhibit important cell surface epitopes and can be used in clinical diagnosis and therapy. We have developed and validated an in vitro evolution-based approach, named differential whole cell SELEX, to generate a panel of high affinity RNA-based aptamers as ligands for a specific cancer cell phenotype (in two different tumor model systems, glioma and NSCLC). We demonstrate that such an approach can be effective for the generation of functional oligonucleotide ligands that are potentially suitable for diagnostic and therapeutic applications.
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