ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
The sea urchin sns5 insulator protects retroviral vectors from chromosomal position effects by maintaining active chromatin structure.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- The Compass-like locus, exclusive to the Ambulacrarians, encodes a chromatin insulator binding protein in the sea urchin embryo.PLoS genetics · 2013Article
- CTF/NF1 transcription factors act as potent genetic insulators for integrating gene transfer vectors.Gene therapy · 2012Article
- Minimizing the unpredictability of transgene expression in plants: the role of genetic insulators.Plant cell reports · 2012Review
- Current advances in retroviral gene therapy.Current gene therapy · 2011Review
- The use of chromatin insulators to improve the expression and safety of integrating gene transfer vectors.Human gene therapy · 2011Review
- The GATA1-HS2 enhancer allows persistent and position-independent expression of a β-globin transgene.PloS one · 2011Article
- A functional screen for regulatory elements that improve retroviral vector gene expression.Blood cells, molecules & diseases · 2010Article
- Promoter activity of the sea urchin (Paracentrotus lividus) nucleosomal H3 and H2A and linker H1 {alpha}-histone genes is modulated by enhancer and chromatin insulator.Nucleic acids research · 2009Article
- Supplying clotting factors from hematopoietic stem cell-derived erythroid and megakaryocytic lineage cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Silencing and position-effect (PE) variegation (PEV), which is due to integration of viral vectors in heterochromatin regions, are considered significant obstacles to obtaining a consistent level of transgene expression in gene therapy. The inclusion of chromatin insulators into vectors has been proposed to counteract this position-dependent variegation of transgene expression. Here, we show that the sea urchin chromatin insulator, sns5, protects a recombinant gamma-retroviral vector from the negative influence of chromatin in erythroid milieu. This element increases the probability of vector expression at different chromosomal integration sites, which reduces both silencing and PEV. By chromatin immunoprecipitation (ChIP) analysis, we demonstrated the specific binding of GATA1 and OCT1 transcription factors and the enrichment of hyperacetylated nucleosomes to sns5 sequences. The results suggest that this new insulator is able to maintain a euchromatin state inside the provirus locus with mechanisms that are common to other characterized insulators. On the basis of its ability to function as barrier element in erythroid milieu and to bind the erythroid specific factor GATA1, the inclusion of sns5 insulator in viral vectors may be of practical benefit in gene transfer applications and, in particular, for gene therapy of erythroid disorders.
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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.