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… 
Improvement of lentiviral vector-mediated gene transduction by genetic engineering of the structural protein Pr55Gag
TLDR
Genetic evidence is provided that the attachment of heterologous myristoylation signals on the amino-terminus of human immunodeficiency virus type 1 Pr55Gag (Gag) can increase the viral yield up to 10-fold, leading to the enhancement of gene transduction in many cell lines.
Recent advances in lentiviral vector development and applications.
TLDR
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.
Integration-deficient lentiviral vectors: a slow coming of age.
TLDR
IDLVs can be converted into replicating episomes, suggesting that if a clinically applicable system can be developed they would also become highly appropriate for stable transduction of proliferating tissues in therapeutic applications.
Lentivirus production is influenced by SV40 large T-antigen and chromosomal integration of the vector in HEK293 cells.
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.
Lentiviral-mediated gene transfer – a patent review
TLDR
Based on the literature, several improvements have been performed regarding the safety, pseudotyping, vector production and purification on the lentivirus system.
A lentiviral vector with novel multiple cloning sites: stable transgene expression in vitro and in vivo.
Lentiviruses: Vectors for Cancer Gene Therapy
TLDR
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.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 245 REFERENCES
A stable system for the high-titer production of multiply attenuated lentiviral vectors.
TLDR
A lentiviral vectors line based on the doxycycline-repressible expression of HIV-1 Rev/Gag/Pol and of the vesicular stomatitis virus G envelope in 293 human embryonic kidney cells is described, which exhibits functional properties similar to those of viruses produced transiently, in particular the ability to transduce nonmitotic targets.
Comparison of lentiviral vector titration methods
TLDR
It is demonstrated that transgenic mRNA levels correlate well with TU and can be used for functional titration of non-fluorescent transgenes, and depending on the experimental set-up one titration method should be preferred over the others.
Effective gene therapy with nonintegrating lentiviral vectors
TLDR
The high efficiency of gene transfer and expression mediated by lentiviruses can be harnessed in vivo without a requirement for vector integration and substantially reduces the risk of insertional mutagenesis.
Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors
TLDR
A human lentiviral (HIV)–based vector that can transduce non-dividing cells in vitro and deliver genes In vivo is described and it is shown that the requirement for lentivirus accessory proteins to establish efficient transduction in vivo is tissue dependent.
Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo
TLDR
A generation of lentiviral vectors with a nonintegrative phenotype of great potential value for secure viral gene transfer in clinical applications is developed, allowing GFP expression in mouse brain cells after the stereotactic injection of IN-deficient vector particles.
A Third-Generation Lentivirus Vector with a Conditional Packaging System
TLDR
It is demonstrated that the requirement for the tat gene can be offset by placing constitutive promoters upstream of the vector transcript, and the improved design presented here should facilitate testing of lentivirus vectors.
Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.
TLDR
Development of clinically acceptable derivatives of the lentiviral vector may enable the sustained delivery of significant amounts of a therapeutic gene product in a wide variety of somatic tissues.
Robust and efficient regulation of transgene expression in vivo by improved tetracycline-dependent lentiviral vectors.
TLDR
A panel of lentiviral vectors displayed tetracycline-regulated transgene expression over two orders of magnitude in bulk, non-selected populations of transduced cells in vitro and in vivo, demonstrating integration of the regulated expression system into long-term repopulating cells.
Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery
TLDR
The inactivation design achieved in this work improves significantly the biosafety of HIV-derived vectors, as it reduces the likelihood that replication-competent retroviruses will originate in the vector producer and target cells, and hampers recombination with wild-type HIV in an infected host.
A new-generation stable inducible packaging cell line for lentiviral vectors.
TLDR
The packaging cell line and all vector producer clones described here were shown to be free from replication-competent recombinants, and from recombinant between packaging and vector constructs that transfer the viral gag-pol genes.
...
1
2
3
4
5
...