ArticleJournal of virology1995
E- vectors: development of novel self-inactivating and self-activating retroviral vectors for safer gene therapy.
Article in Journal of virology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 65 citations in OpenAlex.
- Avian iPSC Derivation to Recover Threatened Wild Species: A Comprehensive Review in Light of Well-Established Protocols.Animals : an open access journal from MDPI · 2024Review
- Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells.Nucleic acids research · 2013Article
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- The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.Microbiology and molecular biology reviews : MMBR · 2009Review
- Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector.Nature biotechnology · 2004Article
- High rates of human immunodeficiency virus type 1 recombination: near-random segregation of markers one kilobase apart in one round of viral replication.Journal of virology · 2003Article
- Human immunodeficiency virus type 1 genetic recombination is more frequent than that of Moloney murine leukemia virus despite similar template switching rates.Journal of virology · 2003Article
- Effects of varying sequence similarity on the frequency of repeat deletion during reverse transcription of a human immunodeficiency virus type 1 vector.Journal of virology · 2002Article
- Zinc finger domain of murine leukemia virus nucleocapsid protein enhances the rate of viral DNA synthesis in vivo.Journal of virology · 2002Article
- Effects of limiting homology at the site of intermolecular recombinogenic template switching during Moloney murine leukemia virus replication.Journal of virology · 2001Article
- Role of murine leukemia virus reverse transcriptase deoxyribonucleoside triphosphate-binding site in retroviral replication and in vivo fidelity.Journal of virology · 2000Article
- Structure-based moloney murine leukemia virus reverse transcriptase mutants with altered intracellular direct-repeat deletion frequencies.Journal of virology · 2000Article
- Utilization of nonviral sequences for minus-strand DNA transfer and gene reconstitution during retroviral replication.Journal of virology · 2000Article
- Structural determinants of murine leukemia virus reverse transcriptase that affect the frequency of template switching.Journal of virology · 2000Article
- Novel Tat-encoding bicistronic human immunodeficiency virus type 1-based gene transfer vectors for high-level transgene expression.Journal of virology · 2000Article
- Split-intron retroviral vectors: enhanced expression with improved safety.Journal of virology · 2000Article
- Development of an in vivo assay to identify structural determinants in murine leukemia virus reverse transcriptase important for fidelity.Journal of virology · 2000Article
- Effect of distance between homologous sequences and 3' homology on the frequency of retroviral reverse transcriptase template switching.Journal of virology · 1999Article
- Development of murine leukemia virus-based self-activating vectors that efficiently delete the selectable drug resistance gene during reverse transcription.Journal of virology · 1999Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We have developed novel self-inactivating and self-activating retroviral vectors based on the previously observed high-frequency deletion of direct repeats. We constructed spleen necrosis virus (SNV)-based viral vectors that contained large direct repeats flanking the viral encapsidation sequence (E). A large proportion of the proviruses in the target cells had E and one copy of the direct repeat deleted. Direct repeats of 1,333 and 788 bp were deleted at frequencies of 93 and 85%, respectively. To achieve a 100% deletion efficiency in target cells after ex vivo infection and drug selection, we constructed a self-activating vector that simultaneously deleted E and reconstituted the neomycin phosphotransferase gene. Selection of the target cells for resistance to G418 (a neomycin analog) ensured that all integrated proviruses had E deleted. The proviruses with E deleted were mobilized by a replication-competent virus 267,000-fold less efficiently than proviruses with E. We named these self-inactivating vectors E- (E-minus) vectors. These vectors should increase the safety of retroviral vector-mediated gene therapy by preventing the spread of vector sequences to nontarget cells in the event of coinfection with helper virus. We propose that direct-repeat deletions occur during RNA-dependent DNA synthesis and suggest that template switches occur without a requirement for RNA breaks. The minimum template dissociation frequency was estimated as 8%/100 bp per replication cycle. These vectors demonstrate that large direct repeats and template-switching properties of reverse transcriptase can be utilized to delete any sequence or reconstitute genes during retroviral replication.
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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.