DNA Nuclear Targeting Sequences for Non-Viral Gene Delivery

Since it is possible that the DNA nuclear Targeting Sequences did have an effect on the amount of transgenes expressed per successfully transfected cell, we looked at the mean fluorescence intensity, but no differences were observed

Ethlinn V. B. van Gaal; Ronald S. Oosting; Roel van Eijk; Marta Bakowska; Dries Feyen; Robbert Jan Kok; Wim E. Hennink; Daan J. A. Crommelin; Enrico Mastrobattista

2011

Scholarcy highlights

  • Non-viral gene therapy is challenged by inefficient delivery at the level of intracellular processing
  • Since it is possible that the DNA nuclear Targeting Sequences did have an effect on the amount of transgenes expressed per successfully transfected cell, we looked at the mean fluorescence intensity, but no differences were observed
  • The suggested mechanism of DTS-induced nuclear uptake is sequence-specific binding of nuclear localization signal-containing transcription factors to plasmid DNA that is delivered into the cytosol, followed by import of the formed TF/plasmid complexes into the nucleus
  • Besides their relevance for improving efficiency of non-viral gene delivery, DTSs are of value from a mechanistic point of view to gain insight into cytonucleoplasmic transport of macromolecules
  • It would be valuable to identify which proteins interact with a DTS and which of these proteins are able to fulfill a role in facilitating nuclear import of the DTS-containing plasmid
  • No significant difference between the two plasmid constructs was observed, regardless of incubation time, and, most importantly, no effect was observed in non-dividing cells
  • Not all proteins that contain a DNA binding domain and an NLS can act to shuttle DNA into the nucleus, and it is thought that the overall organization and structure of the DNA-TF complex might be important
  • Studies performed by Gonçalves et al show that optimization of the DNA nuclear Targeting Sequences sequence is important and that spacing between repetitive binding sites has a strong effect on transfection efficiency

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