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Human gene therapy. Clinical development2018; 29(2); 101-112; doi: 10.1089/humc.2017.143

Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model.

Abstract: The authors are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of interleukin-1 receptor antagonist (IL-1Ra), and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene transfer on a scale proportional to the human knee, a frequent site of OA incidence, studies were focused on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, a functional ceiling dose of ∼5 × 10 viral genomes was previously identified, which elevated the steady state levels of eqIL-1Ra in synovial fluids by >40-fold over endogenous production for at least 6 months. Here, using an osteochondral fragmentation model of early OA, the functional capacity of scAAV.IL-1Ra gene-delivery was examined in equine joints over a period of 12 weeks. In the disease model, transgenic eqIL-1Ra expression was several fold higher than seen previously in healthy joints, and correlated directly with the severity of joint pathology at the time of treatment. Despite wide variation in expression, the steady-state eqIL-1Ra in synovial fluids exceeded that of IL-1 by >400-fold in all animals, and a consistent treatment effect was observed. This included a 30-40% reduction in lameness and ∼25% improvement in total joint pathology by both magnetic resonance imaging and arthroscopic assessments, which included reduced joint effusion and synovitis, and improved repair of the osteochondral lesion. No vector-related increase in eqIL-1Ra levels in blood or urine was noted. Cumulatively, these studies in the equine model indicate scAAV.IL-1Ra administration is reasonably safe and capable of sustained therapeutic IL-1Ra production intra-articularly in joints of human scale. This profile supports consideration for human testing in OA.
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Publication Date: 2018-06-06 PubMed ID: 29869535PubMed Central: PMC6007806DOI: 10.1089/humc.2017.143Google Scholar: Lookup
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  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper details experiments that used self-complementary adeno-associated virus (scAAV) as a vehicle to introduce interleukin-1 receptor antagonist (IL-1Ra) genes into horse’s bodies for the sake of treating osteoarthritis (OA).

Experimental Procedure

  • The researchers used AAV2.5 capsid and equine IL-1Ra, similar to human IL-1Ra, as a transgene to conduct this study.
  • To conduct the study on a scale similar to human joints, they focused on the joints of horse’s forelimbs.
  • Earlier studies had shown that a functional dose of about 5 x 10 viral genomes elevated the levels of equine IL-1Ra production by over 40 times for at least 6 months.
  • In this study, the researchers sought to validate the efficacy of gene-delivery using scAAV.IL-1Ra over a period of 12 weeks, using an osteochondral fragmentation model of early OA.

Results and Observations

  • Within the disease model, the expression of transgenic eqIL-1Ra was found to be much higher than previously observed in healthy joints, and the expression level directly correlated with the severity of joint pathology at the time of treatment.
  • No matter the variance in expression, eqIL-1Ra levels in synovial fluids were observed to be greater than IL-1 by over 400 times in all animals.
  • More specifically, a consistent treatment effect included a 30-40% decrease in lameness and approximately a 25% improvement in total joint pathology. This was observed through MRIs and arthroscopic assessments, which noted less joint effusion and synovitis, and improved repair of the osteochondral lesion.
  • No increase in eqIL-1Ra levels within the blood or urine was noted that could be traced back to the vector.

Conclusions

  • Overall, the trials conducted in the equine model indicated that scAAV.IL-1Ra administration was relatively safe and effective at sustainably producing therapeutic IL-1Ra intra-articularly in joints the size of human ones.
  • These results suggest scAAV.IL-1Ra could be considered for human trials in treating OA.

Cite This Article

APA
Watson Levings RS, Smith AD, Broome TA, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA, Foremny GB, Evans CH, Morton AJ, Winter M, Dark MJ, Nickerson DM, Colahan PT, Ghivizzani SC. (2018). Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model. Hum Gene Ther Clin Dev, 29(2), 101-112. https://doi.org/10.1089/humc.2017.143

Publication

Human gene therapy. Clinical development
ISSN: 2324-8645
NlmUniqueID: 101607433
Country: United States
Language: English
Volume: 29
Issue: 2
Pages: 101-112

Researcher Affiliations

Watson Levings, Rachael S
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Smith, Andrew D
  • 2 Department of Large Animal Clinical Sciences, University of Florida , Gainesville, Florida.
Broome, Ted A
  • 2 Department of Large Animal Clinical Sciences, University of Florida , Gainesville, Florida.
Rice, Brett L
  • 2 Department of Large Animal Clinical Sciences, University of Florida , Gainesville, Florida.
Gibbs, Eric P
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Myara, David A
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Hyddmark, E Viktoria
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Nasri, Elham
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Zarezadeh, Ali
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Levings, Padraic P
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Lu, Yuan
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
White, Margaret E
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Dacanay, E Anthony
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Foremny, Gregory B
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.
Evans, Christopher H
  • 3 Rehabilitation Medicine Research Center, Mayo Clinic , Rochester, Minnesota.
Morton, Alison J
  • 2 Department of Large Animal Clinical Sciences, University of Florida , Gainesville, Florida.
Winter, Mathew
  • 4 Department of Small Animal Clinical Sciences, University of Florida , Gainesville, Florida.
Dark, Michael J
  • 5 Department of Infectious Diseases and Pathology, University of Florida , Gainesville, Florida.
Nickerson, David M
  • 6 Department of Statistics and Actuarial Science, University of Florida , Gainesville, Florida.
Colahan, Patrick T
  • 2 Department of Large Animal Clinical Sciences, University of Florida , Gainesville, Florida.
Ghivizzani, Steven C
  • 1 Department of Orthopedics and Rehabilitation, University of Florida , Gainesville, Florida.

MeSH Terms

  • Animals
  • Dependovirus / genetics
  • Disease Models, Animal
  • Gene Transfer Techniques / adverse effects
  • Genetic Therapy
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Horses
  • Humans
  • Injections, Intra-Articular
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Knee / pathology
  • Osteoarthritis / genetics
  • Osteoarthritis / pathology
  • Osteoarthritis / therapy

Conflict of Interest Statement

C.H.E. and S.C.G. are inventors on several patents and patent applications describing cell- and gene-based therapies for arthritis and connective tissue disorders.

References

This article includes 36 references
  1. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ.. Arthritis Rheum 2012 Jun;64(6):1697-707.
    pmc: PMC3366018pubmed: 22392533doi: 10.1002/art.34453google scholar: lookup
  2. Olson SA, Horne P, Furman B, Huebner J, Al-Rashid M, Kraus VB, Guilak F. The role of cytokines in posttraumatic arthritis.. J Am Acad Orthop Surg 2014 Jan;22(1):29-37.
    pubmed: 24382877doi: 10.5435/JAAOS-22-01-29google scholar: lookup
  3. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.. Nat Rev Rheumatol 2011 Jan;7(1):33-42.
    pubmed: 21119608doi: 10.1038/nrrheum.2010.196google scholar: lookup
  4. Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: role in biology.. Annu Rev Immunol 1998;16:27-55.
    pubmed: 9597123doi: 10.1146/annurev.immunol.16.1.27google scholar: lookup
  5. Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, Conrozier T, Loeuille D, Kivitz AJ, Silver D, Appleton BE. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study.. Arthritis Rheum 2009 Mar 15;61(3):344-52.
    pubmed: 19248129doi: 10.1002/art.24096google scholar: lookup
  6. Kay JD, Gouze E, Oligino TJ, Gouze JN, Watson RS, Levings PP, Bush ML, Dacanay A, Nickerson DM, Robbins PD, Evans CH, Ghivizzani SC. Intra-articular gene delivery and expression of interleukin-1Ra mediated by self-complementary adeno-associated virus.. J Gene Med 2009 Jul;11(7):605-14.
    pmc: PMC2876984pubmed: 19384892doi: 10.1002/jgm.1334google scholar: lookup
  7. Watson RS, Broome TA, Levings PP, Rice BL, Kay JD, Smith AD, Gouze E, Gouze JN, Dacanay EA, Hauswirth WW, Nickerson DM, Dark MJ, Colahan PT, Ghivizzani SC. scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints.. Gene Ther 2013 Jun;20(6):670-7.
    pmc: PMC3577988pubmed: 23151520doi: 10.1038/gt.2012.81google scholar: lookup
  8. Evans CH, Ghivizzani SC, Robbins PD. Arthritis gene therapy and its tortuous path into the clinic.. Transl Res 2013 Apr;161(4):205-16.
    pmc: PMC3602127pubmed: 23369825doi: 10.1016/j.trsl.2013.01.002google scholar: lookup
  9. Madry H, Cucchiarini M. Advances and challenges in gene-based approaches for osteoarthritis.. J Gene Med 2013 Oct;15(10):343-55.
    pubmed: 24006099doi: 10.1002/jgm.2741google scholar: lookup
  10. Goodrich LR, Grieger JC, Phillips JN, Khan N, Gray SJ, McIlwraith CW, Samulski RJ. scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy.. Gene Ther 2015 Jul;22(7):536-45.
    pmc: PMC5567794pubmed: 25902762doi: 10.1038/gt.2015.21google scholar: lookup
  11. Goater J, Müller R, Kollias G, Firestein GS, Sanz I, O'Keefe RJ, Schwarz EM. Empirical advantages of adeno associated viral vectors in vivo gene therapy for arthritis.. J Rheumatol 2000 Apr;27(4):983-9.
    pubmed: 10782827
  12. Mason JB, Gurda BL, Engiles JB, Hankenson KD, Wilson JM, Richardson DW. Multiple recombinant adeno-associated viral vector serotypes display persistent in vivo gene expression in vector-transduced rat stifle joints.. Hum Gene Ther Methods 2013 Jun;24(3):185-94.
    pmc: PMC3732130pubmed: 23659250doi: 10.1089/hgtb.2012.199google scholar: lookup
  13. Guy J, Qi X, Muzyczka N, Hauswirth WW. Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve.. Arch Ophthalmol 1999 Jul;117(7):929-37.
    pubmed: 10408459doi: 10.1001/archopht.117.7.929google scholar: lookup
  14. Vincent KR, Conrad BP, Fregly BJ, Vincent HK. The pathophysiology of osteoarthritis: a mechanical perspective on the knee joint.. PM R 2012 May;4(5 Suppl):S3-9.
    pmc: PMC3635670pubmed: 22632700doi: 10.1016/j.pmrj.2012.01.020google scholar: lookup
  15. Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse - a review.. Vet J 2006 Jan;171(1):51-69.
    pubmed: 16427582doi: 10.1016/j.tvjl.2004.07.008google scholar: lookup
  16. McCarty DM, Monahan PE, Samulski RJ. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis.. Gene Ther 2001 Aug;8(16):1248-54.
    pubmed: 11509958doi: 10.1038/sj.gt.3301514google scholar: lookup
  17. McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ. Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo.. Gene Ther 2003 Dec;10(26):2112-8.
    pubmed: 14625565doi: 10.1038/sj.gt.3302134google scholar: lookup
  18. Watson Levings RS, Broome TA, Smith AD, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA, Foremny GB, Evans CH, Morton AJ, Winter M, Dark MJ, Nickerson DM, Colahan PT, Ghivizzani SC. Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.. Hum Gene Ther Clin Dev 2018 Jun;29(2):90-100.
    pmc: PMC6007808pubmed: 29869540doi: 10.1089/humc.2017.142google scholar: lookup
  19. Li C, Diprimio N, Bowles DE, Hirsch ML, Monahan PE, Asokan A, Rabinowitz J, Agbandje-McKenna M, Samulski RJ. Single amino acid modification of adeno-associated virus capsid changes transduction and humoral immune profiles.. J Virol 2012 Aug;86(15):7752-9.
    pmc: PMC3421647pubmed: 22593151doi: 10.1128/JVI.00675-12google scholar: lookup
  20. Frisbie DD, Ghivizzani SC, Robbins PD, Evans CH, McIlwraith CW. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene.. Gene Ther 2002 Jan;9(1):12-20.
    pubmed: 11850718doi: 10.1038/sj.gt.3301608google scholar: lookup
  21. Ishihara A, Bartlett JS, Bertone AL. Inflammation and immune response of intra-articular serotype 2 adeno-associated virus or adenovirus vectors in a large animal model.. Arthritis 2012;2012:735472.
    pmc: PMC3263587pubmed: 22288012doi: 10.1155/2012/735472google scholar: lookup
  22. Ortved K, Wagner B, Calcedo R, Wilson J, Schaefer D, Nixon A. Humoral and cell-mediated immune response, and growth factor synthesis after direct intraarticular injection of rAAV2-IGF-I and rAAV5-IGF-I in the equine middle carpal joint.. Hum Gene Ther 2015 Mar;26(3):161-71.
    pmc: PMC4367237pubmed: 25705927doi: 10.1089/hum.2014.050google scholar: lookup
  23. Keegan KG, MacAllister CG, Wilson DA, Gedon CA, Kramer J, Yonezawa Y, Maki H, Pai PF. Comparison of an inertial sensor system with a stationary force plate for evaluation of horses with bilateral forelimb lameness.. Am J Vet Res 2012 Mar;73(3):368-74.
    pubmed: 22369528doi: 10.2460/ajvr.73.3.368google scholar: lookup
  24. Keegan KG, Wilson DA, Kramer J, Reed SK, Yonezawa Y, Maki H, Pai PF, Lopes MA. Comparison of a body-mounted inertial sensor system-based method with subjective evaluation for detection of lameness in horses.. Am J Vet Res 2013 Jan;74(1):17-24.
    pubmed: 23270341doi: 10.2460/ajvr.74.1.17google scholar: lookup
  25. Winter MD. The basics of musculoskeletal magnetic resonance imaging: terminology, imaging sequences, image planes, and descriptions of basic pathologic change.. Vet Clin North Am Equine Pract 2012 Dec;28(3):599-616.
    pubmed: 23177134doi: 10.1016/j.cveq.2012.09.001google scholar: lookup
  26. Smith AD, Morton AJ, Winter MD, Colahan PT, Ghivizzani S, Brown MP, Hernandez JA, Nickerson DM. MAGNETIC RESONANCE IMAGING SCORING OF AN EXPERIMENTAL MODEL OF POST-TRAUMATIC OSTEOARTHRITIS IN THE EQUINE CARPUS.. Vet Radiol Ultrasound 2016 Sep;57(5):502-14.
    pmc: PMC5016209pubmed: 27198611doi: 10.1111/vru.12369google scholar: lookup
  27. Roemer FW, Kassim Javaid M, Guermazi A, Thomas M, Kiran A, Keen R, King L, Arden NK. Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI.. Osteoarthritis Cartilage 2010 Oct;18(10):1269-74.
    pubmed: 20691796doi: 10.1016/j.joca.2010.07.008google scholar: lookup
  28. Sun J, Hua B, Chen X, Samulski RJ, Li C. Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.. Hum Gene Ther 2017 Aug;28(8):654-666.
    pmc: PMC5568595pubmed: 28478688doi: 10.1089/hum.2017.016google scholar: lookup
  29. Elsaid KA, Zhang L, Shaman Z, Patel C, Schmidt TA, Jay GD. The impact of early intra-articular administration of interleukin-1 receptor antagonist on lubricin metabolism and cartilage degeneration in an anterior cruciate ligament transection model.. Osteoarthritis Cartilage 2015 Jan;23(1):114-21.
    pmc: PMC4275352pubmed: 25219670doi: 10.1016/j.joca.2014.09.006google scholar: lookup
  30. Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair.. J Clin Invest 2002 Jun;109(11):1405-15.
    pmc: PMC151001pubmed: 12045254doi: 10.1172/JCI15681google scholar: lookup
  31. Geusens P, Emans PJ, de Jong JJ, van den Bergh J. NSAIDs and fracture healing.. Curr Opin Rheumatol 2013 Jul;25(4):524-31.
    pubmed: 23680778doi: 10.1097/BOR.0b013e32836200b8google scholar: lookup
  32. Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions.. Nat Rev Rheumatol 2012 Jan 31;8(3):133-43.
    pubmed: 22293759doi: 10.1038/nrrheum.2012.1google scholar: lookup
  33. Matzelle MM, Gallant MA, Condon KW, Walsh NC, Manning CA, Stein GS, Lian JB, Burr DB, Gravallese EM. Resolution of inflammation induces osteoblast function and regulates the Wnt signaling pathway.. Arthritis Rheum 2012 May;64(5):1540-50.
    pmc: PMC4015187pubmed: 22139865doi: 10.1002/art.33504google scholar: lookup
  34. Chang J, Liu F, Lee M, Wu B, Ting K, Zara JN, Soo C, Al Hezaimi K, Zou W, Chen X, Mooney DJ, Wang CY. NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation.. Proc Natl Acad Sci U S A 2013 Jun 4;110(23):9469-74.
    pmc: PMC3677422pubmed: 23690607doi: 10.1073/pnas.1300532110google scholar: lookup
  35. Arend WP, Welgus HG, Thompson RC, Eisenberg SP. Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist.. J Clin Invest 1990 May;85(5):1694-7.
    pmc: PMC296623pubmed: 2139669doi: 10.1172/JCI114622google scholar: lookup
  36. Arend WP. The balance between IL-1 and IL-1Ra in disease.. Cytokine Growth Factor Rev 2002 Aug-Oct;13(4-5):323-40.
    pubmed: 12220547doi: 10.1016/s1359-6101(02)00020-5google scholar: lookup

Citations

This article has been cited 23 times.
  1. Li X, Shen L, Deng Z, Huang Z. New treatment for osteoarthritis: Gene therapy. Precis Clin Med 2023 Jun;6(2):pbad014.
    doi: 10.1093/pcmedi/pbad014pubmed: 37333626google scholar: lookup
  2. Floramo JS, Molchanov V, Liu H, Liu Y, Craig SEL, Yang T. An Integrated View of Stressors as Causative Agents in OA Pathogenesis. Biomolecules 2023 Apr 22;13(5).
    doi: 10.3390/biom13050721pubmed: 37238590google scholar: lookup
  3. Uebelhoer M, Lambert C, Grisart J, Guse K, Plutizki S, Henrotin Y. Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review. Front Med (Lausanne) 2023;10:1148623.
    doi: 10.3389/fmed.2023.1148623pubmed: 37077668google scholar: lookup
  4. Evans CH, Ghivizzani SC, Robbins PD. Osteoarthritis gene therapy in 2022. Curr Opin Rheumatol 2023 Jan 1;35(1):37-43.
    doi: 10.1097/BOR.0000000000000918pubmed: 36508307google scholar: lookup
  5. Shi G, Long Z, De la Vega RE, Behfar A, Moran SL, Evans C, Zhao C. Purified exosome product enhances chondrocyte survival and regeneration by modulating inflammation and promoting chondrogenesis. Regen Med 2023 Jan;18(1):55-71.
    doi: 10.2217/rme-2022-0132pubmed: 36255073google scholar: lookup
  6. Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR. Gene therapy approaches for equine osteoarthritis. Front Vet Sci 2022;9:962898.
    doi: 10.3389/fvets.2022.962898pubmed: 36246316google scholar: lookup
  7. Crabtree E, Uribe K, Smith SM, Roberts D, Salmon JH, Bower JJ, Song L, Bastola P, Hirsch ML, Gilger BC. Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy. PLoS One 2022;17(8):e0270972.
    doi: 10.1371/journal.pone.0270972pubmed: 35980983google scholar: lookup
  8. Abdul TY, Hawse GP, Smith J, Sellon JL, Abdel MP, Wells JW, Coenen MJ, Evans CH, De La Vega RE. Prevalence of AAV2.5 neutralizing antibodies in synovial fluid and serum of patients with osteoarthritis. Gene Ther 2023 Aug;30(7-8):587-591.
    doi: 10.1038/s41434-022-00326-5pubmed: 35260797google scholar: lookup
  9. Senter R, Boyce R, Repic M, Martin EW, Chabicovsky M, Langevin-Carpentier G, Bédard A, Bodick N. Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model. Hum Gene Ther 2022 May;33(9-10):541-549.
    doi: 10.1089/hum.2021.131pubmed: 34963343google scholar: lookup
  10. Schulze-Tanzil G. Experimental Therapeutics for the Treatment of Osteoarthritis. J Exp Pharmacol 2021;13:101-125.
    doi: 10.2147/JEP.S237479pubmed: 33603501google scholar: lookup
  11. Chen Q, Luo H, Zhou C, Yu H, Yao S, Fu F, Seeley R, Ji X, Yang Y, Chen P, Jin H, Tong P, Chen D, Wu C, Du W, Ruan H. Comparative intra-articular gene transfer of seven adeno-associated virus serotypes reveals that AAV2 mediates the most efficient transduction to mouse arthritic chondrocytes. PLoS One 2020;15(12):e0243359.
    doi: 10.1371/journal.pone.0243359pubmed: 33320893google scholar: lookup
  12. Braucke AFGV, Frederiksen NL, Berg LC, Aarsvold S, Müller FC, Boesen MP, Lindegaard C. Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue. Animals (Basel) 2020 Mar 18;10(3).
    doi: 10.3390/ani10030506pubmed: 32197454google scholar: lookup
  13. Moss KL, Jiang Z, Dodson ME, Linardi RL, Haughan J, Gale AL, Grzybowski C, Engiles JE, Stefanovski D, Robinson MA, Ortved KF. Sustained Interleukin-10 Transgene Expression Following Intra-Articular AAV5-IL-10 Administration to Horses. Hum Gene Ther 2020 Jan;31(1-2):110-118.
    doi: 10.1089/hum.2019.195pubmed: 31773987google scholar: lookup
  14. Daniels O, Frisch J, Venkatesan JK, Rey-Rico A, Schmitt G, Cucchiarini M. Effects of rAAV-Mediated sox9 Overexpression on the Biological Activities of Human Osteoarthritic Articular Chondrocytes in Their Intrinsic Three-Dimensional Environment. J Clin Med 2019 Oct 7;8(10).
    doi: 10.3390/jcm8101637pubmed: 31591319google scholar: lookup
  15. Patel JM, Saleh KS, Burdick JA, Mauck RL. Bioactive factors for cartilage repair and regeneration: Improving delivery, retention, and activity. Acta Biomater 2019 Jul 15;93:222-238.
    doi: 10.1016/j.actbio.2019.01.061pubmed: 30711660google scholar: lookup
  16. Evans C. Editorial: Arthritis Gene Therapy Using Interleukin-1 Receptor Antagonist. Arthritis Rheumatol 2018 Nov;70(11):1699-1701.
    doi: 10.1002/art.40675pubmed: 30035385google scholar: lookup
  17. Zhou K, Yuan M, Sun J, Zhang F, Li X, Xiao X, Wu X. Co-delivery of IL-1Ra and SOX9 via AAV inhibits inflammation and promotes cartilage repair in surgically induced osteoarthritis animal models. Gene Ther 2025 May;32(3):211-222.
    doi: 10.1038/s41434-025-00515-ypubmed: 39833570google scholar: lookup
  18. Luo S, Jiang H, Li Q, Yang S, Yu X, Xu X, Xie Q, Ke X, Zheng Q. The Intra-Articular Delivery of a Low-Dose Adeno-Associated Virus-IL-1 Receptor Antagonist Vector Alleviates the Progress of Arthritis in an Osteoarthritis Rat Model. Pharmaceutics 2024 Nov 25;16(12).
    doi: 10.3390/pharmaceutics16121518pubmed: 39771498google scholar: lookup
  19. Lane NE, Simon LS, Tambiah J. Slow acting medications for progressive and painful knee osteoarthritis. How do we assess the benefit to risk of these potentially novel therapies?. Osteoarthr Cartil Open 2025 Mar;7(1):100546.
    doi: 10.1016/j.ocarto.2024.100546pubmed: 39737142google scholar: lookup
  20. Kim YS, Steward N, Kim A, Fehle I, Guilak F. Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4. Tissue Eng Part A 2025 Feb;31(3-4):174-183.
    doi: 10.1089/ten.TEA.2024.0163pubmed: 39007506google scholar: lookup
  21. Velot É, Balmayor ER, Bertoni L, Chubinskaya S, Cicuttini F, de Girolamo L, Demoor M, Grigolo B, Jones E, Kon E, Lisignoli G, Murphy M, Noël D, Vinatier C, van Osch GJVM, Cucchiarini M. Women's contribution to stem cell research for osteoarthritis: an opinion paper. Front Cell Dev Biol 2023;11:1209047.
    doi: 10.3389/fcell.2023.1209047pubmed: 38174070google scholar: lookup
  22. Doron G, Wood LB, Guldberg RE, Temenoff JS. Poly(ethylene glycol)-Based Hydrogel Microcarriers Alter Secretory Activity of Genetically Modified Mesenchymal Stromal Cells. ACS Biomater Sci Eng 2023 Nov 13;9(11):6282-6292.
    doi: 10.1021/acsbiomaterials.3c00954pubmed: 37906515google scholar: lookup
  23. Thampi P, Seabaugh KA, Pezzanite LM, Chu CR, Phillips JN, Grieger JC, McIlwraith CW, Samulski RJ, Goodrich LR. A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis. Gene Ther 2023 Dec;30(12):792-800.
    doi: 10.1038/s41434-023-00420-2pubmed: 37696981google scholar: lookup
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