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The Nuclear Pore Complex: The Gateway to Successful Nonviral Gene Delivery

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Abstract

One of the limiting steps in the efficiency of nonviral gene delivery is transport of genetic material across the nuclear membrane. Trafficking of nuclear proteins from the cytoplasm into the nucleus occurs via the nuclear pore complex and is mediated by nuclear localization signals and their nuclear receptors. Several strategies employing this transport mechanism have been designed and explored to improve nonviral gene delivery. In this article, we review the mechanism of nuclear import through the nuclear pore complex and the strategies used to facilitate nuclear import of exogenous DNA and improve gene expression.

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Abbreviations

CAS:

cellular apoptosis susceptibility gene

CF:

cytoplasmic filament

CR:

cytoplasmic ring

GEF:

GDP–GTP exchange factor

GR:

glucocorticoid receptor

HEAT:

histidine, glutamic acid, alanine, and threonine

hnRNP:

heterogeneous ribonucleoprotein

IBB:

importin β binding domain

NE:

nuclear envelope

NES:

nuclear export signal

NLS:

nuclear localization signal

NPC:

nuclear pore complex

PEG:

polyethylene glycol

PEI:

polyethylenimine

PLL:

poly-l-lysine

PNA:

peptide nucleic acid

POM:

pore membrane proteins

SMGD:

steroid-mediated gene delivery

Vpr:

viral protein R

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Authors and Affiliations

  1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands

    Marieke A. E. M. van der Aa, Enrico Mastrobattista, Wim E. Hennink & Daan J. A. Crommelin

  2. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands

    Ronald S. Oosting

  3. Section Radiation and Isotopes for Health, Department of Radiation, Radioisotopes and Reactors, Faculty of Applied Sciences, Delft University of Technology, Mekelweg 15, 2629 JB, Delft, The Netherlands

    Gerben A. Koning

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  1. Marieke A. E. M. van der Aa
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  5. Gerben A. Koning
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  6. Daan J. A. Crommelin
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Correspondence to Daan J. A. Crommelin.

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van der Aa, M.A.E.M., Mastrobattista, E., Oosting, R.S. et al. The Nuclear Pore Complex: The Gateway to Successful Nonviral Gene Delivery. Pharm Res 23, 447–459 (2006). https://doi.org/10.1007/s11095-005-9445-4

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  • DOI: https://doi.org/10.1007/s11095-005-9445-4

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