ArticleProceedings of the National Academy of Sciences of the United States of America2005
Gene transfer to human joints: progress toward a gene therapy of arthritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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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.
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Who cites it
73 citing papers in PubMed, 213 citations in OpenAlex.
- Clinical responses to gene therapy in joints of two subjects with rheumatoid arthritis.Human gene therapy · 2009Trial
- Sex matters: mechanistic insights into sex-driven patterns of autoimmunity and implications for pharmacotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- What's next for osteoarthritis gene therapy?Frontiers in bioengineering and biotechnology · 2026Review
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
- Orthobiologics in knee osteoarthritis, dream or reality?Archives of orthopaedic and trauma surgery · 2024Review
- Contextual AI models for single-cell protein biology.Nature methods · 2024Article
- Contextual AI models for single-cell protein biology.bioRxiv : the preprint server for biology · 2024Article
- Streamlined, single-step non-viral CRISPR-Cas9 knockout strategy enhances gene editing efficiency in primary human chondrocyte populations.Arthritis research & therapy · 2024Article
- Gene Delivery to Chondrocytes.Advances in experimental medicine and biology · 2023Article
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- Gene therapy for bone healing: lessons learned and new approaches.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Immunoengineering the next generation of arthritis therapies.Acta biomaterialia · 2021Review
- Orthopaedic Gene Therapy: Twenty-Five Years On.JBJS reviews · 2021Article
- Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2020Review
- Reduced hypertrophy in vitro after chondrogenic differentiation of adult human mesenchymal stem cells following adenoviral SOX9 gene delivery.BMC musculoskeletal disorders · 2020Article
- The vicissitudes of gene therapy.Bone & joint research · 2019Article
- A Synthetic Gene Circuit for Self-Regulating Delivery of Biologic Drugs in Engineered Tissues.Tissue engineering. Part A · 2019Article
- Editorial: Arthritis Gene Therapy Using Interleukin-1 Receptor Antagonist.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Gene Delivery to Joints by Intra-Articular Injection.Human gene therapy · 2018Review
- Biological Treatment Approaches for Degenerative Disc Disease: A Review of Clinical Trials and Future Directions.Cureus · 2016Review
13 more citing papers are in PubMed but not listed here.
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 at 2 institutions in 1 country.
Funding
Abstract
This article describes the clinical application of gene therapy to a nonlethal disease, rheumatoid arthritis (RA). Intraarticular transfer of IL-1 receptor antagonist (IL-1Ra) cDNA reduces disease in animal models of RA. Whether this procedure is safe and feasible in humans was addressed in a phase I clinical study involving nine postmenopausal women with advanced RA who required unilateral sialastic implant arthroplasty of the 2nd-5th metacarpophalangeal (MCP) joints. Cultures of autologous synovial fibroblasts were established and divided into two. One was transduced with a retrovirus carrying IL-1Ra cDNA; the other provided untransduced, control cells. In a dose escalation, double-blinded fashion, two MCP joints were injected with transduced cells, and two MCP joints received control cells. One week later, injected joints were resected and examined for evidence of successful gene transfer and expression by using RT-PCR, ex vivo production of IL-1Ra, in situ hybridization, and immunohistochemistry. All subjects tolerated the protocol well, without adverse events. Unlike control joints, those receiving transduced cells gave positive RT-PCR signals. Synovia that were recovered from the MCP joints of intermediate and high dose subjects produced elevated amounts of IL-1Ra (P = 0.01). Clusters of cells expressing high levels of IL-1Ra were present on synovia of transduced joints. No adverse events occurred. Thus, it is possible to transfer a potentially therapeutic gene safely to human rheumatoid joints and to obtain intraarticular, transgene expression. This conclusion justifies additional efficacy studies and encourages further development of genetic approaches to the treatment of arthritis and related disorders.
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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.