Gene delivery by lentivirus vectors

@article{Cockrell2007GeneDB,
  title={Gene delivery by lentivirus vectors},
  author={Adam S. Cockrell and Tal Kafri},
  journal={Molecular Biotechnology},
  year={2007},
  volume={36},
  pages={184-204}
}
The capacity to efficiently transduce nondividing cells, shuttle large genetic payloads, and maintain stable long-term transgene expression are attributes that have brought lentiviral vectors to the forefront of gene delivery vehicles for research and therapeutic applications in a clinical setting. Our discussion initiates with advances in lentiviral vector development and how these sophisticated lentiviral vectors reflect improvements in safety, regarding the prevention of replication… 
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314 Citations
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314 Citations

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Recent advances underscore the improved safety and efficacy of LVs, which allow for site-specific gene correction or addition in predefined chromosomal loci, with important implications for clinical trials.
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TLDR
It is found that lentiviral vectors result in minimal infectious particle production from single copy integrants in HEK293, and T-Ag does not exert its role at the level of transcriptional activity of the vector; rather, it seems to impose an indirect effect on the cell thereby enabling lentivir vector production.
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Based on the literature, several improvements have been performed regarding the safety, pseudotyping, vector production and purification on the lentivirus system.
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Partitioned engineered backbones containing the essential proteins needed for reverse transcription and integration and separate elements for the transgene payload provide a 3 or 4 safety designed components that when transduced into transient producer cells yield high titre vectors.
Superior lentiviral vectors designed for BSL-0 environment abolish vector mobilization.
TLDR
It is demonstrated that configuring the internal vector expression cassette in opposite orientation to the LTRs abolishes mobilization of SIN vectors, an additional PKR-dependent SIN mechanism that abolishes vector mobilization from integrated and episomal SIN lentiviral vectors.
The Impact of Peptide Insertions on Adeno-Associated Viral Vector Fate
TLDR
This study shows for the first time, that the inserted ligand both alters the mechanism of AAV vector internalization and determines the efficiency of cell entry and nuclear delivery of vector genomes in rAAV2.
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