Αρχειοθήκη ιστολογίου

Παρασκευή 13 Απριλίου 2018

Efficient gene silencing in brain tumors with hydrophobically modified siRNAs

Glioblastoma (GBM) is the most common and lethal form of primary brain tumor with dismal median and two-year survivals of 14.5 months and 18%, respectively. The paucity of new therapeutic agents stems from the complex biology of a highly adaptable tumor that uses multiple survival and proliferation mechanisms to circumvent current treatment approaches. Here, we investigated the potency of a new generation of small interfering RNAs (siRNAs) to silence gene expression in orthotopic brain tumors generated by transplantation of human glioma stem-like cells (GSCs) in athymic nude mice. We demonstrate that cholesterol-conjugated, nuclease-resistant siRNAs (Chol-hsiRNAs) decrease mRNA and silence luciferase expression by 90% in vitro in GBM neurospheres. Furthermore, Chol-hsiRNAs distribute broadly in brain tumors after a single intratumoral injection, achieving sustained and potent (>45% mRNA and >90% protein) tumor-specific gene silencing. This readily available platform is sequence-independent and can be adapted to target one or more candidate GBM driver genes, providing a straightforward means of modulating GBM biology in vivo.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2vfvISO

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