ArticleRetrovirology2007
Design of a trans protease lentiviral packaging system that produces high titer virus.
Article in Retrovirology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
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- Highly efficient in vitro and in vivo delivery of functional RNAs using new versatile MS2-chimeric retrovirus-like particles.Molecular therapy. Methods & clinical development · 2015Article
- Mononuclear cells from dedifferentiation of mouse myotubes display remarkable regenerative capability.Stem cells (Dayton, Ohio) · 2014Article
- Article
- Replication competent virus as an important source of bias in HIV latency models utilizing single round viral constructs.Retrovirology · 2014Article
- Analysis of partial recombinants in lentiviral vector preparations.Human gene therapy methods · 2014Article
- Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.Nature medicine · 2014Article
- HIV-1 Nef inhibits Protease activity and its absence alters protein content of mature viral particles.PloS one · 2014Article
- Sca-1 is involved in the adhesion of myosphere cells to αVβ3 integrin.Biology open · 2012Article
- Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice.Cell · 2010Article
- Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres.The American journal of pathology · 2010Article
- Adult muscle 'stem' cells can be sustained in culture as free-floating myospheres.Experimental cell research · 2010Article
- Cross-packaging of genetically distinct mouse and primate retroviral RNAs.Retrovirology · 2009Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe structural and enzymatic proteins of the human immunodeficiency virus (HIV) are initially generated as two long polyproteins encoded from overlapping reading frames, one producing the structural proteins (Gag) and the second producing both structural and enzymatic proteins (Gag-Pol). The Gag to Gag-Pol ratio is critical for the proper assembly and maturation of viral particles. To minimize the risk of producing a replication competent lentivirus (RCL), we developed a "super-split" lentiviral packaging system in which Gag was separated from Pol with minimal loss of transducibility by supplying protease (PR) in trans independently of both Gag and Pol.
resultsIn developing this "super-split" packaging system, we incorporated several new safety features that include removing the Gag/Gag-Pol frameshift, splitting the Gag, PR, and reverse transcriptase/integrase (RT/IN) functions onto separate plasmids, and greatly reducing the nucleotide sequence overlap between vector and Gag and between Gag and Pol. As part of the construction of this novel system, we used a truncated form of the accessory protein Vpr, which binds the P6 region of Gag, as a vehicle to deliver both PR and RT/IN as fusion proteins to the site of viral assembly and budding. We also replaced wt PR with a slightly less active T26S PR mutant in an effort to prevent premature processing and cytoxicity associated with wt PR. This novel "super-split" packaging system yielded lentiviral titers comparable to those generated by conventional lentiviral packaging where Gag-Pol is supplied intact (1.0 x 106 TU/ml, unconcentrated).
conclusionHere, we were able to create a true "split-function" lentiviral packaging system that has the potential to be used for gene therapy applications. This novel system incorporates many new safety features while maintaining high titers. In addition, because PR is supplied in trans, this unique system may also provide opportunities to examine viral protein processing and maturation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.