Nucleocytoplasmic transport of plasmid DNA: a perilous journey from the cytoplasm to the nucleus
Open accessAbstract
Nonviral vectors represent a promising approach for the safe delivery of therapeutic DNA in genetic and acquired human diseases. Before synthetic vector systems can be used for clinical applications, their limited efficacy must be addressed. At the cellular level, successful gene transfer is dependent on several additional factors including DNA uptake, release from the DNA-vector complex, and nucleocytoplasmic transport. This paper reviews the major metabolic and physical impediments that plasmid DNA vectorized by synthetic vectors encounters between the cytosol and the nucleus. Plasmid DNA that escapes the endolysosomal compartment encounters the diffusional and metabolic barriers of the cytoplasm, reducing the number of intact plasmids that reach the nuclear envelope. Nuclear translocation of DNA requires either the disassembly of the nuclear envelope during cell division or active nuclear transport via the nuclear pore complex. In the nucleus, plasmid DNA is relatively stable, but its transcription and its fate during cell division are still debated. A better understanding of the cellular and molecular basis of nonviral gene transfer during nucleocytoplasmic trafficking may provide strategies to overcome those obstacles that limit the efficiency of nonviral gene delivery. We review some of the current methods of gene transfer mediated by synthetic vectors, highlighting systems that exploit our actual knowledge of the nucleocytoplasmic transport of plasmid DNA.
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Disruption or reorganization of actin cytoskeleton, or depletion of keratin and vimentin, significantly increases diffusion of gene payloads.
“Disruption or reorganization of the actin cytoskeleton, or depletion of keratin and vimentin in cells, significantly increases the diffusion of gene payloads [190–192].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [190]
Once released into cytosol, non-viral vectors loaded with CRISPR/Cas9 need to overcome additional barriers including mesh-like cytoskeleton and nucleolytic enzymes within cytosolic milieu.
“Once released into the cytosol, non-viral vectors loaded with CRISPR/Cas9 system need to overcome additional barriers in the cytosol, including the mesh-like cytoskeleton and nucleolytic enzymes within the cytosolic milieu [190].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [190]
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- Authors
- Lechardeur, D., & Lukacs, G. L.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children, Program in Cell and Lung Biology, Department of Biochemistry and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1X8 Canada.
- ORCID
- Lechardeur, Delphine
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2006-09
- Volume
- 17
- Issue
- 9
- Pages
- 882-889
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W2084327544
- Cited by
- 99
- References
- 95
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 7
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- plasmid DNA, nuclear transport, non-viral gene delivery, synthetic vectors, nuclear translocation, nuclear pore complex, endolysosomal escape, DNA uptake, cell division
- MeSH terms
- Biological Transport, Cell Nucleus, Cytoplasm, DNA, Plasmids
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