Joint MBG & iNANO Specialized Lecture: Aptamers for Cancer cell-Targeted Delivery of Therapeutic miRNAs
Dr. Vittorio de Franciscis, Institute of Experimental Endocrinology and Oncology - CNR Naples, Italy
Info about event
iNANO meeting room 1590-213, Gustav Wieds Vej 14, 8000 Aarhus C
Dr. Vittorio de Franciscis, Research Director, Institute of Experimental Endocrinology and Oncology - CNR Naples, Italy
Aptamers for Cancer cell-Targeted Delivery of Therapeutic miRNAs
Glioblastoma (GBM) is the most common primary brain tumor and one of the most lethal kind of cancer. Recent studies have led to the hypothesis that GBM is sustained by a small population of cancer stem cells (glioblastoma stem cells, GSCs). GSCs retain stem cell properties including self-renewal and multipotency and are a major cause of tumor progression and recurrence.
Recently, it has been shown the great potential of microRNAs (miRNAs) and miRNA inhibitors (antimiRs) as cancer therapeutics. However, a major obstacle to their translation to the clinic is the lack of a reliable way for their specific delivery.
In this respect, nucleic acid aptamers are emerging as a very promising class of carrier molecules. We have recently characterized two nuclease resistant RNA-aptamers, named GL21.T and Gint4.T that bind and inhibit Axl and PDGFRß respectively. By using different approaches, we have generated multi-functional RNA-based chimeras constituted of internalizing aptamers (GL21.T and Gint4) conjugated to therapeutic “oncosuppressors” miRNAs or anti-miRNAs directed against microRNAs upregulated in glioblastoma and GSCs.
Treating target GSCs with aptamer-miRNA/antimiR conjugates modulate the expression of miRNA targets leading to anti-cancer effects. In addition, we show that more conjugates, used in combination, further improve their biological effect leading to the suppression of tumor sphere formation.
Results provide the rationale for the design of combined gene therapies selectively targeting cancer stem cells.
|Host: Professor Peter Andreasen, Department of Molecular Biology and Genetics, Aarhus University