ArticleGene therapy2009
Transgene optimization significantly improves SIN vector titers, gp91phox expression and reconstitution of superoxide production in X-CGD cells.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07476183 (A Phase 1, Open-label, Single-arm Study of APR 2020 in Transfusion Dependent, Steroid Resistant Pediatric and Adolescent Subjects With RPS19 Deficient Diamond Blackfan Anemia by Transplantation of Autologous CD34+ Stem Cells Transduced With CLIN LV EFS coRPS19 PRE*), which is not on this map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
A Phase 1, Open-label, Single-arm Study of APR 2020 in Transfusion Dependent, Steroid Resistant Pediatric and Adolescent Subjects With RPS19 Deficient Diamond Blackfan Anemia by Transplantation of Autologous CD34+ Stem Cells Transduced With CLIN LV EFS coRPS19 PRE* (APR-2020)
Who cites it
32 citing papers in PubMed.
- Successful gene therapy of Diamond-Blackfan anemia in a mouse model and human CD34Haematologica · 2022Article
- Increased CFTR expression and function from an optimized lentiviral vector for cystic fibrosis gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- Correction of X-CGD patient HSPCs by targeted CYBB cDNA insertion using CRISPR/Cas9 with 53BP1 inhibition for enhanced homology-directed repair.Gene therapy · 2021Article
- Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned.Cell stem cell · 2017Review
- Advances of gene therapy for primary immunodeficiencies.F1000Research · 2016Review
- Design of a regulated lentiviral vector for hematopoietic stem cell gene therapy of globoid cell leukodystrophy.Molecular therapy. Methods & clinical development · 2015Article
- Dual-regulated lentiviral vector for gene therapy of X-linked chronic granulomatosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Generation of X-CGD cells for vector evaluation from healthy donor CD34(+) HSCs by shRNA-mediated knock down of gp91(phox).Molecular therapy. Methods & clinical development · 2014Article
- Transgene expression in various organs post BM-HSC transplantation.Stem cell research · 2014Article
- Comparison of transduction efficiency among various lentiviruses containing GFP reporter in bone marrow hematopoietic stem cell transplantation.Experimental hematology · 2013Article
- Gene therapy on the move.EMBO molecular medicine · 2013Review
- From bench to bedside: preclinical evaluation of a self-inactivating gammaretroviral vector for the gene therapy of X-linked chronic granulomatous disease.Human gene therapy. Clinical development · 2013Article
- Alpharetroviral vector-mediated gene therapy for X-CGD: functional correction and lack of aberrant splicing.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Biosafety features of lentiviral vectors.Human gene therapy · 2013Review
- Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Physiological regulation of transgene expression by a lentiviral vector containing the A2UCOE linked to a myeloid promoter.Gene therapy · 2012Article
- Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Correction of murine Rag1 deficiency by self-inactivating lentiviral vector-mediated gene transfer.Leukemia · 2011Article
- Review
- Lentiviral vector design and imaging approaches to visualize the early stages of cellular reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene therapy has proven to be of potential value for the correction of inherited hematopoietic disorders. However, the occurrence of severe side effects in some of the clinical trials has questioned the safety of this approach and has hampered the use of long terminal repeat-driven vectors for the treatment of a large number of patients. The development of self-inactivating (SIN) vectors with reduced genotoxicity provides an alternative to the currently used vectors. Our initial attempts to use SIN vectors for the correction of a myeloid disorder, chronic granulomatous disease, failed due to low vector titers and poor transgene expression. The optimization of the transgene cDNA (gp91(phox)) resulted in substantially increased titers and transgene expression. Most notably, transgene optimization significantly improved expression of a second cistron located downstream of gp91(phox). Thus, optimization of the transgene sequence results in higher expression levels and increased therapeutic index allowing the use of low vector copy numbers per transduced cell and weaker internal promoters.
Indexed as
Identifiers
18784749What 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.