ArticleNucleic acids research1997
Evaluation of beta-globin gene therapy constructs in single copy transgenic mice.
Article in Nucleic acids research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 40 citations in OpenAlex.
- Animal models of β-hemoglobinopathies: utility and limitations.Journal of blood medicine · 2016Review
- Beta-globin LCR and intron elements cooperate and direct spatial reorganization for gene therapy.PLoS genetics · 2008Article
- Retrovirus silencer blocking by the cHS4 insulator is CTCF independent.Nucleic acids research · 2003Article
- Evaluation of optimal expression cassette in retrovirus vector for beta-thalassemia gene therapy.Molecular biotechnology · 2003Article
- Retrovirus vector silencing is de novo methylase independent and marked by a repressive histone code.The EMBO journal · 2000Article
- Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Amelioration of retroviral vector silencing in locus control region beta-globin-transgenic mice and transduced F9 embryonic cells.Journal of virology · 1999Article
- Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Microinjection of cre recombinase RNA induces site-specific recombination of a transgene in mouse oocytes.Nucleic acids research · 1998Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Effective gene therapy constructs based on retrovirus or adeno-associated virus vectors will require regulatory elements that direct expression of genes transduced at single copy. Most beta-globin constructs designed for therapy of beta-thalassemias are regulated by the 5'HS2 component of the locus control region (LCR). Here we show that a human beta-globin gene flanked by two small 5'HS2 core elements or flanked by a 5'HS3 (footprints 1-3) core and a 5'HS2 core are not reproducibly expressed in single copy transgenic mice. In addition, low copy transgene concatamers that contain only dimer 5'HS2 cores fail to express, whereas those that contain monomer 5'HS2 cores express at 14% per copy. These data suggest that spacing between HS cores is crucial for LCR activity. We therefore constructed a novel 3.0 kb LCR cassette in which the 5'HS2, 5'HS3 and 5'HS4 cores are each separated by approximately 700 bp. When linked to the 815 bp beta-globin promoter this LCR directs 45% levels of expression from four independent single copy transgenes. However, the 3.0 kb LCR linked to the 265 bp promoter expresses variable levels, averaging 18%, from three single copy transgenes. Our findings suggest that sequences in the distal promoter play a role in single copy transgene activation and that larger LCR and promoter elements are most suitable for gene therapy applications.
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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.