ArticleThe journal of gene medicine2009
Intra-articular gene delivery and expression of interleukin-1Ra mediated by self-complementary adeno-associated virus.
Article in The journal of gene medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.Tissue engineering. Part A · 2025Article
- Ferroptosis in osteoarthritis: metabolic reprogramming, immunometabolic crosstalk, and targeted intervention strategies.Frontiers in immunology · 2025Review
- Global seroprevalence of neutralizing antibodies against adeno-associated virus serotypes used for human gene therapies.Molecular therapy. Methods & clinical development · 2024Article
- Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.Reviews in endocrine & metabolic disorders · 2024Review
- Engineering approaches for RNA-based and cell-based osteoarthritis therapies.Nature reviews. Rheumatology · 2024Review
- A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis.Gene therapy · 2023Article
- Review
- Serotype-specific transduction of canine joint tissue explants and cultured monolayers by self-complementary adeno-associated viral vectors.Gene therapy · 2023Article
- Gene therapy approaches for equine osteoarthritis.Frontiers in veterinary science · 2022Review
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends.Frontiers in pharmacology · 2021Review
- Review
- Sustained Interleukin-10 Transgene Expression Following Intra-Articular AAV5-IL-10 Administration to Horses.Human gene therapy · 2020Article
- IL-1RA suppresses esophageal cancer cell growth by blocking IL-1α.Journal of clinical laboratory analysis · 2019Article
- Genetic modification of scAAV-equine-BMP-2 transduced bone-marrow-derived mesenchymal stem cells before and after cryopreservation: An "off-the-shelf" option for fracture repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019Article
- Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.Human gene therapy. Clinical development · 2018Article
- The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018Review
- Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model.Human gene therapy. Clinical development · 2018Article
- Gene therapy for chondral and osteochondral regeneration: is the future now?Cellular and molecular life sciences : CMLS · 2018Review
- Gene Delivery to Joints by Intra-Articular Injection.Human gene therapy · 2018Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe adeno-associated virus (AAV) has many safety features that favor its use in the treatment of arthritic conditions; however, the conventional, single-stranded vector is inefficient for gene delivery to fibroblastic cells that primarily populate articular tissues. This has been attributed to the inability of these cells to convert the vector to a double-stranded form. To overcome this, we evaluated double-stranded self-complementary (sc) AAV as a vehicle for intra-articular gene delivery.
methodsConventional and scAAV vectors were used to infect lapine articular fibroblasts in culture to determine transduction efficiency, transgene expression levels, and nuclear trafficking. scAAV containing the cDNA for interleukin (IL)-1 receptor antagonist (Ra) was delivered to the joints of naïve rabbits and those with IL-1beta-induced arthritis. From lavage of the joint space, levels of transgenic expression and persistence were measured by enzyme-linked immunosorbent assay. Infiltrating leukocytes were quantified using a hemocytometer.
resultsTransgene expression from scAAV had an earlier onset and was approximately 25-fold greater than conventional AAV despite the presence of similar numbers of viral genomes in the nuclei of infected cells. Fibroblasts transduced with scAAV produced amounts of IL1-Ra comparable to those transduced with adenoviral and lentiviral vectors. IL1-Ra was present in lavage fluid of most animals for 2 weeks in sufficient quantities to inhibit inflammation of the IL-1beta-driven model. Once lost, neither subsequent inflammatory events, nor re-administration of the virus could re-establish transgene expression.
conclusionsscAAV-mediated intra-articular gene transfer is robust and similarly efficient in both normal and inflamed joints; the resulting transgenic expression is sufficient to achieve biological relevance in joints of human proportion.
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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.