Progress and prospects: Nuclear import of nonviral vectors

A. P. Lam, D. A. Dean

Research output: Contribution to journalReview articlepeer-review

166 Scopus citations


The nuclear envelope represents a key barrier to successful nonviral transfection and gene therapy both in vitro and in vivo. Although the main purpose of the nuclear envelope is to partition the cell to maintain cytoplasmic components in the cytoplasm and nuclear components, most notably genomic DNA, in the nucleus, this function poses a problem for transfections in which exogenous DNA is delivered into the cytoplasm. After delivery to the cytoplasm, nucleic acids rapidly become complexed with cellular proteins that mediate interactions with the cellular machinery for trafficking. Thus, it is these proteins that, in essence, control the nuclear import of DNA, and we must also understand their activities in cells. In this review, we will discuss the principles of nuclear import of proteins and DNA-protein complexes, as well as the various approaches that investigators have used to improve nuclear targeting of plasmids. These approaches include complexation of plasmids with peptides, native and engineered proteins, ligands and polymers, as well as the inclusion of transcription factor-binding sites for general and cell-specific delivery.

Original languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalGene therapy
Issue number4
StatePublished - Apr 2010


  • Importin
  • Karyopherin
  • Nonviral gene transfer
  • Nuclear localization signal
  • Nuclear pore complex
  • Plasmid

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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