ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Computational design and application of endogenous promoters for transcriptionally targeted gene therapy for rheumatoid arthritis.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3.Immune network · 2025Article
- Recent Advances in Studies of Serum Amyloid A: Implications in Inflammation, Immunity and Tumor Metastasis.International journal of molecular sciences · 2025Review
- Bub1 suppresses inflammatory arthritis-associated bone loss in mice through inhibition of TNFα-mediated osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions.Frontiers in cardiovascular medicine · 2023Review
- Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures.PLoS pathogens · 2021Article
- The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment.Scientific reports · 2019Article
- Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitmentTheranostics · 2018Article
- Serum Amyloid A3 Gene Expression in Adipocytes is an Indicator of the Interaction with Macrophages.Scientific reports · 2016Article
- Suppression of the inflammatory response by disease-inducible interleukin-10 gene therapy in a three-dimensional micromass model of the human synovial membrane.Arthritis research & therapy · 2016Article
- Gene profiling of Chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis.Arthritis and rheumatism · 2012Article
- Rho kinase inhibitor Y-27632 prolongs the life span of adult human keratinocytes, enhances skin equivalent development, and facilitates lentiviral transduction.Tissue engineering. Part A · 2012Article
- A novel hybrid promoter responsive to pathophysiological and pharmacological regulation.Journal of molecular medicine (Berlin, Germany) · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The promoter regions of genes that are differentially regulated in the synovial membrane during the course of rheumatoid arthritis (RA) represent attractive candidates for application in transcriptionally targeted gene therapy. In this study, we applied an unbiased computational approach to define proximal-promoters from a gene expression profiling study of murine experimental arthritis. Synovium expression profiles from progressing stages of collagen-induced arthritis (CIA) were classified into six distinct groups using k-means clustering. Using an algorithm based on local over-representation and comparative genomics, we identified putatively functional transcription factor-binding sites (TFBS) in TATA-dependent proximal-promoters. Applying a filter based on spacing between TATA box and transcription start site (TSS) combined with the presence of over-represented nuclear factor kappaB (NFkappaB), AP-1, or CCAAT/enhancer-binding protein beta (C/EBPbeta) sites, 382 candidate murine and human promoters were reduced to 66, corresponding to 45 genes. In vitro, 9 out of 10 computationally defined promoter regions conferred cytokine-inducible expression in murine cells and human synovial fibroblasts. Under these conditions, the serum amyloid A3 (Saa3) promoter showed the strongest transcriptional induction and strength. We applied this promoter for driving therapeutically efficacious levels of the interleukin-1 receptor antagonist (Il1rn) in a disease-regulated fashion. These results demonstrate the value of bioinformatics for guiding the selection of endogenous promoters for transcriptionally targeted gene therapy.
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