A gene delivery system containing nuclear localization signal: increased nucleus import and transfection efficiency with the assistance of RanGAP1
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NLSs have been introduced into vectors to facilitate transportation to nucleus.
“Inspired by the active transportation process of proteins to nucleus, nuclear localization sequences (NLSs) have been introduced into the vectors to facilitate transportation to nucleus [195–197].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [196]
Cites
Fang, J. Q., Nakamura, H., & Maeda, H. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.04.009 · Cited by 3,573 · see citing works
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · see citing works
He, C., Hu, Y., Yin, L., Tang, C., & Yin, C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.01.065 · Cited by 2,607 · see citing works
The Basic Science of Gene Therapy
Mulligan, R. C. (1993) · Science · doi:10.1126/science.8493530 · Cited by 1,734 · see citing works
Synthetic DNA delivery systems
Luo, D., & Saltzman, W. M. (2000) · Nature Biotechnology · doi:10.1038/71889 · Cited by 1,625 · see citing works
Classical Nuclear Localization Signals: Definition, Function, and Interaction with Importin α
Lange, A., Mills, R. E., Lange, C. J., Stewart, M., Devine, S. E., & Corbett, A. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600026200 · Cited by 1,168 · see citing works
Identification of different roles for RanGDP and RanGTP in nuclear protein import.
Görlich, D., Panté, N., Kutay, U., Aebi, U., & Bischoff, F. R. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00943.x · Cited by 648 · see citing works
Structural Biology of Nucleocytoplasmic Transport
Cook, A. G., Bono, F., Jínek, M., & Conti, E. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052705.161529 · Cited by 526 · see citing works
Non-viral gene therapy: polycation-mediated DNA delivery
Thomas, M., & Klibanov, A. M. (2003) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-003-1321-8 · Cited by 482 · see citing works
Barriers to Nonviral Gene Delivery
Wiethoff, C. M., & Middaugh, C. R. (2003) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10286 · Cited by 480 · see citing works
Simple Modifications of Branched PEI Lead to Highly Efficient siRNA Carriers with Low Toxicity
Zintchenko, A., Philipp, A. B., Dehshahri, A., & Wagner, E. (2008) · Bioconjugate Chemistry · doi:10.1021/bc800065f · Cited by 464 · see citing works
The nuclear pore complex: nucleocytoplasmic transport and beyond
Fahrenkrog, B., & Aebi, U. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1230 · Cited by 421 · see citing works
Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions
Raı́ces, M., & D’Angelo, M. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3461 · Cited by 373 · see citing works
Woodle, M. C., Engbers, C. M., & Zalipsky, S. (1994) · Bioconjugate Chemistry · doi:10.1021/bc00030a001 · Cited by 361 · see citing works
Dissection of a Nuclear Localization Signal
Hodel, M. R., Corbett, A. H., & Hodel, A. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008522200 · Cited by 338 · see citing works
Functional Architecture of the Nuclear Pore Complex
Grossman, E., Medalia, O., & Zwerger, M. (2012) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-050511-102328 · Cited by 275 · see citing works
The nuclear pore complex: mediator of translocation between nucleus and cytoplasm
Allen, T., Cronshaw, J. M., Bagley, S., et al. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.10.1651 · Cited by 264 · see citing works
China approves first gene therapy
Pearson, S., Jia, H., & Kandachi, K. (2004) · Nature Biotechnology · doi:10.1038/nbt0104-3 · Cited by 256 · see citing works
Non-viral gene therapy: Gains and challenges of non-invasive administration methods
Földvári, M., Chen, D.-W., Nafissi, N., Calderon-Nieva, D., Narsineni, L., & Rafiee, A. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.12.012 · Cited by 240 · see citing works
Self-citationNon-Viral Gene Delivery Methods
Wang, W., Li, W., Ma, N., & Steinhoff, G. (2013) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201011314010008 · Cited by 229 · see citing works
Self-citationCortez, M. A., Godbey, W. T., Fang, Y., Payne, M. E., Cafferty, B. J., Kosakowska, K. A., & Grayson, S. M. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b00980 · Cited by 228 · see citing works
RanGAP mediates GTP hydrolysis without an arginine finger
Seewald, M. J., Körner, C., Wittinghofer, A., & Vetter, I. R. (2002) · Nature · doi:10.1038/415662a · Cited by 226 · see citing works
Mitosis enhances transgene expression of plasmid delivered by cationic liposomes
Tseng, W., Haselton, F. R., & Giorgio, T. D. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00039-1 · Cited by 221 · see citing works
Chono, S., Tanino, T., Seki, T., & Morimoto, K. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.59.1.0010 · Cited by 190 · see citing works
Targeted Drug Delivery : Concepts and Design
Jain, S., & Devarajan, P. V. (2014) · Advances in delivery science and technology · doi:10.1007/978-3-319-11355-5 · Cited by 168 · see citing works
Nuclear localization signals for four distinct karyopherin-β nuclear import systems
Soniat, M. M., & Chook, Y. M. (2015) · Biochemical Journal · doi:10.1042/bj20150368 · Cited by 165 · see citing works
Importin-β modulates the permeability of the nuclear pore complex in a Ran-dependent manner
Lowe, A. R., Tang, J. H., Yassif, J. M., et al. (2015) · eLife · doi:10.7554/elife.04052 · Cited by 146 · see citing works
Hodel, A. E., Harreman, M. T., Pulliam, K. F., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601718200 · Cited by 111 · see citing works
Endoprotease-Mediated Intracellular Protein Delivery Using Nanocapsules
Biswas, A., Joo, K., Liu, J., Zhao, M., Fan, G., Wang, P., Gu, Z., & Tang, Y. (2011) · ACS Nano · doi:10.1021/nn1031005 · Cited by 103 · see citing works
Non-Viral Gene Delivery Methods
Wang, W., Li, W., Ma, N., et al. (2013) · Current Pharmaceutical Biotechnology · doi:10.2174/138920113804805278 · Cited by 97 · see citing works
Self-citationDelgado, D., Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., Echevarrı́a, E., de Garibay, A. P. R., Rodríguez, J. M., & Solinís, M. Á. (2012) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.12.052 · Cited by 91 · see citing works
The molecular architecture of the plant nuclear pore complex
Tamura, K., & Hara‐Nishimura, I. (2012) · Journal of Experimental Botany · doi:10.1093/jxb/ers258 · Cited by 91 · see citing works
Hébert, E. (2003) · Biology of the Cell · doi:10.1016/s0248-4900(03)00007-8 · Cited by 90 · see citing works
Huebsch, N., & Mooney, D. J. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.01.023 · Cited by 81 · see citing works
A Code for RanGDP Binding in Ankyrin Repeats Defines a Nuclear Import Pathway
Lu, M. M., Žák, J., Chen, S., Sánchez‐Pulido, L., Severson, D. T., Endicott, J., Ponting, C. P., Schofield, C. J., & Lü, X. (2014) · Cell · doi:10.1016/j.cell.2014.05.006 · Cited by 76 · see citing works
Hu, Q., Wang, J., Shen, J., Liu, M., Jin, X., Tang, G., & Chu, P. K.-H. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.10.023 · Cited by 73 · see citing works
Ku, H.-K., Lim, H.-M., Oh, K. H., et al. (2012) · Analytical Biochemistry · doi:10.1016/j.ab.2012.10.045 · Cited by 65 · see citing works
Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis
Matchett, K. B., McFarlane, S., Hamilton, S., Eltuhamy, Y. S. A., Davidson, M. A., Murray, J. T., Faheem, A., & El‐Tanani, M. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-8032-8_15 · Cited by 60 · see citing works
Xu, Y., Liang, W., Qiu, Y., et al. (2016) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.6b00338 · Cited by 59 · see citing works
Zhang, H., & Vinogradov, S. V. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.01.020 · Cited by 52 · see citing works
Rodríguez, J. A. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.03.005 · Cited by 46 · see citing works
In vitro inhibition of the replication of classical swine fever virus by porcine Mx1 protein
He, D., Zhang, X.-M., Liu, K., Pang, R., Zhao, J., Zhou, B., & Chen, P. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.01.020 · Cited by 45 · see citing works
Understanding Nonviral Nucleic Acid Delivery with Quantum Dot-FRET Nanosensors
Grigsby, C. L., Ho, Y., & Leong, K. W. (2012) · Nanomedicine · doi:10.2217/nnm.12.28 · Cited by 33 · see citing works
Chen, K., Chen, Q., Wang, K., et al. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.05.060 · Cited by 27 · see citing works
Self-citationWang, L., Chen, G., Chen, K., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3149 · Cited by 25 · see citing works
Self-citationCancer Biology and the Nuclear Envelope
Schirmer, E. C., & Heras, J. I. D. L. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4899-8032-8 · Cited by 22 · see citing works
Tong, J., Sun, D., Yang, C., et al. (2016) · Research in Veterinary Science · doi:10.1016/j.rvsc.2016.01.008 · Cited by 22 · see citing works
Yoo, H. S., & Jeong, S. Y. (2006) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.09.013 · Cited by 17 · see citing works
Gene therapy as a potential tool for treating neuroblastoma—a focused review
Kumar, M. D., Dravid, A. N., Kumar, A., & Sen, D. (2016) · Cancer Gene Therapy · doi:10.1038/cgt.2016.16 · Cited by 14 · see citing works
Zhang, H., Liang, Z., Li, W., et al. (2013) · Journal of Bioactive and Compatible Polymers · doi:10.1177/0883911513483507 · Cited by 11 · see citing works
Self-citationTargeted Delivery of Nucleic Acid Therapeutics via Nonviral Vectors
Kapoor, M., & Burgess, D. J. (2014) · Advances in delivery science and technology · doi:10.1007/978-3-319-11355-5_8 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
- 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
- ORCID
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review