Analyzer · Sparsifire

Analyze how specific documents activate the features of the SAE. Select a dataset, a run and a document to begin.

Dataset

SAE Model

Document

Active Features

1554

MIN ACTIVATION

0.0

Details List

#1295 Feature 1295

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#1501 Feature 1501

#2521 Feature 2521

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#503 Feature 503

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#1489 Feature 1489

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#23 Neuronal Circuitry and Cellular Processes

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#1302 Sensing and Detection Technologies

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#2118 Feature 2118

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#261 Feature 261

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#2563 Feature 2563

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#474 Surgical Procedures & Gastrointestinal Issues

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#2322 Feature 2322

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#1540 Feature 1540

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#1506 Justification/Rationale for Actions

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#2121 Feature 2121

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Document Content

Intracellular barriers to non-viral gene transfer.
Non-viral vector mediated gene transfer, compared to viral vector mediated one, is a promising tool for the safe delivery of therapeutic DNA in genetic and acquired human diseases. Although the lack of specific immune response favor the clinical application of non-viral vectors, comprising of an expression cassette complexed to cationic liposome or cationic polymer, the limited efficacy and short duration of transgene expression impose major hurdles in the widespread application of non-viral gene therapy. The trafficking of transgene, complexed with chemical vectors, has been the subject of intensive investigations to improve our understanding of cellular and extracellular barriers impeding gene delivery. Here, we review those physical and metabolic impediments that account, at least in part, for the inefficient translocation of transgene into the nucleus of target cells. Following the internalization of the DNA-polycation complex by endocytosis, a large fraction is targeted to the lysosomal compartment by default. Since the cytosolic release of heterelogous DNA is a prerequisite for nuclear translocation, entrapment and degradation of plasmid DNA in endo-lysosomes constitute a major impediment to efficient gene transfer. Only a small fraction of internalized plasmid DNA penetrates the cytoplasm. Plasmid DNA encounters the diffusional and metabolic barriers of the cytoplasm, further decreasing the number of intact plasmid molecules reaching the nuclear pore complex (NPC), the gateway of nucleosol. Nuclear translocation of DNA requires either the disassembly of the nuclear envelope or active nuclear transport via the NPC. Comparison of viral and plasmid DNA cellular trafficking should reveal strategies that viruses have developed to overcome those cellular barriers that impede non-viral DNA delivery in gene therapy attempts.

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