Cited by 37RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryNuclear Structure and Function

A gene delivery system containing nuclear localization signal: increased nucleus import and transfection efficiency with the assistance of RanGAP1

Chen, Kang, Guo, Lingling, Zhang, Jiulong, Chen, Qing, Wang, Kuanglei, Li, Chenxi, Li, Weinan, Qiao, Mingxi +3 more·2017·Acta Biomaterialia

Abstract

In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1.Statement of significance The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. The transfection of PAMS/DNA/10NLS had less dependence on the breakdown of nuclear envelope. Both the nuclear import and transfection efficiency of PAMS/DNA/10NLS were higher in RanGAP1 overexpressed cells than that in normal cells. Moreover, the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice.

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Crossref · 10.1016/j.actbio.2016.11.004

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Cited by

Authors
Chen, K., Guo, L., Zhang, J., Chen, Q., Wang, K., Li, C., Li, W., Qiao, M., Zhao, X., Hu, H., & Chen, D.
Affiliations
Shenyang Pharmaceutical University (CN)
Corresponding author
  • Hu, Haiyang
  • Chen, Dawei
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2017-01
Volume
48
Pages
215-226
ISSN
1742-7061 (ISSN-L)
OpenAlex
W2547707860
Cited by
37
References
51
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 5
FWCI
2.77
Type
journal article
Language
en
Open access
closed
Locations
  • Acta Biomaterialia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
gene delivery, nuclear localization signal, RanGAP1, nuclear import, transfection efficiency, importins, GTPase-activating protein, in vivo transfection, acid degradation, nuclear envelope permeability, gene therapy vectors
MeSH terms
Animals, Cell Line, Cell Nucleus, DNA, Female, Mice, Inbred BALB C, Mice, Nude, Nuclear Envelope, Particle Size, Transfection, Nuclear Localization Signals, GTPase-Activating Proteins, Active Transport, Cell Nucleus, Dendrimers, Static Electricity

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