Effective mRNA Inhibition in PANC-1 Cells in Vitro Mediated via an mPEG-SeSe-PEI Delivery System

Biol Pharm Bull. 2016 May 1;39(5):680-8. doi: 10.1248/bpb.b15-00645. Epub 2016 Mar 5.

Abstract

RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG-SeSe-PEI, was developed and its efficacy evaluated. We prepared three mPEG-SeSe-PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG11.6-SeSe-PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG11.6-SeSe-PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG11.6-SeSe-PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).

MeSH terms

  • Cell Line, Tumor
  • Gene Silencing
  • Gene Transfer Techniques*
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / genetics*
  • Humans
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / chemistry
  • Polymers / administration & dosage*
  • Polymers / chemistry
  • RNA Interference
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Small Interfering / administration & dosage*

Substances

  • Polymers
  • RNA, Messenger
  • RNA, Small Interfering
  • polyetherimide
  • Polyethylene Glycols
  • monomethoxypolyethylene glycol
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)