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Progress and prospects: nuclear import of nonviral vectors

Gene Therapy volume 17, pages 439–447 (2010)Cite this article

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Abstract

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. Keywords:nonviral gene transfer∣plasmid∣nuclear pore complex∣importin∣nuclear localization signal∣karyopherin.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL, USA

    A P Lam

  2. Departments of Pediatrics and Biomedical Engineering, University of Rochester, Rochester, NY, USA

    D A Dean

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  1. A P Lam
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Correspondence to D A Dean.

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Lam, A., Dean, D. Progress and prospects: nuclear import of nonviral vectors. Gene Ther 17, 439–447 (2010). https://doi.org/10.1038/gt.2010.31

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