Human-derived NLS enhance the gene transfer efficiency of chitosan

Diogo B Bitoque, Joana Morais, Ana V Oliveira, Raquel L Sequeira, Sofia M Calado, Tiago M Fortunato, Sonia Simão, Ana M Rosa da Costa, Gabriela A Silva

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Abstract

Nuclear import is considered one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA. In this work, human-derived endogenous NLS peptides based on Insulin Growth Factor Binding Proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors.

Original languageEnglish
Article numberBSR20201026
JournalBioscience Reports
Volume41
Issue number1
Early online date11 Dec 2020
DOIs
Publication statusPublished - Jan 2021

Keywords

  • gene therapy
  • chitosan
  • nuclear localization signals
  • IGFBP
  • HEK293T cells

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