Gene silencing and antitumoral effects of Eg5 or Ran siRNA oligoaminoamide polyplexes

Drug Delivery and Translational Research
Daniel EdingerErnst Wagner

Abstract

Two antitumoral siRNAs (directed against target genes Eg5 and Ran) complexed with one of three sequence-defined cationic oligomers were compared in gene silencing in vitro and antitumoral in vivo efficacy upon intratumoral injection. Two lipo-oligomers (T-shape 49, i-shape 229) and the three-arm oligomer 386 were chosen because of their high efficiency in previous marker gene silencing screens. The oligomers showed very similar target-specific gene knockdown in murine neuroblastoma cells. Silencing persisted only for a short period (maximum on day 1 at mRNA and day 2 at protein level) triggering siRNA specific in vitro tumor cell killing. The fastest onset of protein knockdown and strongest antitumoral effect was mediated by oligomer 386. Tumor growth reduction in vivo was evaluated in the subcutaneous Neuro2A mouse model. Intratumoral injections of either Eg5 or Ran siRNA/oligomer 49 polyplexes led to reduced tumor growth and prolonged survival of mice compared to control siRNA and buffer treatment. Target knockdown was evidenced in tumors by mitotic Aster formation for Eg5 knockdown and apoptotic TUNEL stain for Ran knockdown. Ran siRNA displayed better antitumoral efficacy and was chosen for in vivo comparison of the oligome...Continue Reading

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Citations

Jun 12, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dian-Jang LeeErnst Wagner
Jun 28, 2018·The Journal of Gene Medicine·Benjamin SteinbornWei Zhang
Jul 29, 2019·International Journal of Pharmaceutics·Ines TruebenbachErnst Wagner
Jan 25, 2021·Biochemical and Biophysical Research Communications·Jianran HuJun Tie

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