FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Gene Ther / scAAVIL-1ra dosing trial in a large animal model and validat...
Gene therapy2015; 22(7); 536-545; doi: 10.1038/gt.2015.21

scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy.

Abstract: A gene therapeutic approach to treat osteoarthritis (OA) appears to be on the horizon for millions of people who suffer from this disease. Previously we described optimization of a scAAVIL-1ra gene therapeutic vector and initially tested this in an equine model verifying long-term intrasynovial IL-1ra protein at therapeutic levels. Using this vector, we carried out a dosing trial in six horses to verify protein levels and establish a dose that would express relevant levels of therapeutic protein for extended periods of time (8 months). A novel arthroscopic procedure used to detect green fluorescence protein (GFP) fluorescence intrasynovially confirmed successful transduction of the scAAVGFP vector in both the synovial and cartilage tissues. No evidence of intra-articular toxicity was detected. Immune responses to vector revealed development of neutralizing antibodies (Nabs) within 2 weeks of administration, which persisted for the duration of the study but did not lower protein expression intra-articularly. Re-dosing with a different serotype to attain therapeutic levels of protein confirmed establishment of successful transduction. This is the first study in an equine model to establish a dosing/redosing protocol, as well as examine the Nab response to capsid and supports further clinical investigation to determine the clinical efficacy of scAAVIL-1ra to treat OA.
Get Full Text
Publication Date: 2015-04-23 PubMed ID: 25902762PubMed Central: PMC5567794DOI: 10.1038/gt.2015.21Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

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.

This study investigated a new gene therapeutic approach to treat osteoarthritis using a therapeutic vector, scAAVIL-1ra, with testing done on horses to monitor therapeutic protein levels over an 8-month period.

Study design and Methodology

  • The researchers created a gene therapeutic vector, scAAVIL-1ra, designed to produce therapeutic levels of anti-inflammatory protein, IL-1ra, directly in the joint. This protein can help treat osteoarthritis by reducing inflammation.
  • The vector was tested on six horses, where the team carried out a dosing trial over an extended period of eight months to monitor the levels of the therapeutic protein produced.

Experimental Procedure

  • A novel arthroscopic procedure was used to detect green fluorescence protein (GFP) fluorescence within the joint. This helped confirm successful transduction of the scAAVGFP vector in both the synovial and cartilage tissues.
  • No signs of toxicity from the procedure were detected in the joint.

Immune Response and Redosing

  • The study also noted the development of neutralizing antibodies (Nabs) within two weeks of administration. These antibodies persisted throughout the study but did not decrease intra-articular protein expression.
  • The researchers followed up with a second dosage using a different serotype. This was to achieve therapeutic levels of protein, thereby confirming the successful establishment of transduction.

Significance and Implications

  • This study is the first of its kind in an equine model to establish a dosing and re-dosing protocol and to examine the Nab response to capsid.
  • The findings suggest the potential of the scAAVIL-1ra gene therapy to treat osteoarthritis, paving the way for further clinical investigations.

Cite This Article

APA
Goodrich LR, Grieger JC, Phillips JN, Khan N, Gray SJ, McIlwraith CW, Samulski RJ. (2015). scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy. Gene Ther, 22(7), 536-545. https://doi.org/10.1038/gt.2015.21

Publication

Gene therapy
ISSN: 1476-5462
NlmUniqueID: 9421525
Country: England
Language: English
Volume: 22
Issue: 7
Pages: 536-545

Researcher Affiliations

Goodrich, L R
  • Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, CO, USA.
Grieger, J C
  • UNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Phillips, J N
  • Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, CO, USA.
Khan, N
  • UNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gray, S J
  • UNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
McIlwraith, C W
  • Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins, CO, USA.
Samulski, R J
  • UNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

MeSH Terms

  • Animals
  • Antibodies, Neutralizing / metabolism
  • Carpal Joints / immunology
  • Carpal Joints / metabolism
  • Carpal Joints / pathology
  • Cartilage, Articular / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Gene Expression / immunology
  • Genetic Therapy
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / immunology
  • Genetic Vectors / therapeutic use
  • Horses
  • Interleukin 1 Receptor Antagonist Protein / immunology
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Osteoarthritis / genetics
  • Osteoarthritis / immunology
  • Osteoarthritis / metabolism
  • Osteoarthritis / therapy
  • Synovial Membrane / metabolism

Grant Funding

  • K08 AR054903 / NIAMS NIH HHS
  • R01 AI072176 / NIAID NIH HHS
  • R01AI072176 / NIAID NIH HHS
  • R01AR064369 / NIAMS NIH HHS
  • 1K08AR054903-01A2 / NIAMS NIH HHS
  • P01HL112761 / NHLBI NIH HHS
  • R01 AR064369 / NIAMS NIH HHS
  • R25 GM089569 / NIGMS NIH HHS
  • P01 HL112761 / NHLBI NIH HHS

Conflict of Interest Statement

. The authors declare no conflict of interest.

References

This article includes 59 references
  1. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, Hawker GA, Henrotin Y, Hunter DJ, Kawaguchi H, Kwoh K, Lohmander S, Rannou F, Roos EM, Underwood M. OARSI guidelines for the non-surgical management of knee osteoarthritis.. Osteoarthritis Cartilage 2014 Mar;22(3):363-88.
    pubmed: 24462672doi: 10.1016/j.joca.2014.01.003google scholar: lookup
  2. Ishijima M, Nakamura T, Shimizu K, Hayashi K, Kikuchi H, Soen S, Omori G, Yamashita T, Uchio Y, Chiba J, Ideno Y, Kubota M, Kurosawa H, Kaneko K. Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center, randomized, open-label, non-inferiority trial.. Arthritis Res Ther 2014 Jan 21;16(1):R18.
    pmc: PMC3979073pubmed: 24443804doi: 10.1186/ar4446google scholar: lookup
  3. Frisbie DD, Kawcak CE, McIlwraith CW, Werpy NM. Evaluation of polysulfated glycosaminoglycan or sodium hyaluronan administered intra-articularly for treatment of horses with experimentally induced osteoarthritis.. Am J Vet Res 2009 Feb;70(2):203-9.
    pubmed: 19231952doi: 10.2460/ajvr.70.2.203google scholar: lookup
  4. Frisbie DD, Kawcak CE, Trotter GW, Powers BE, Walton RM, McIlwraith CW. Effects of triamcinolone acetonide on an in vivo equine osteochondral fragment exercise model.. Equine Vet J 1997 Sep;29(5):349-59.
    pubmed: 9306060doi: 10.1111/j.2042-3306.1997.tb03138.xgoogle scholar: lookup
  5. Baltzer AW, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis.. Osteoarthritis Cartilage 2009 Feb;17(2):152-60.
    pubmed: 18674932doi: 10.1016/j.joca.2008.06.014google scholar: lookup
  6. Abate M, Schiavone C, Salini V. Hyaluronic acid in ankle osteoarthritis: why evidence of efficacy is still lacking?. Clin Exp Rheumatol 2012 Mar-Apr;30(2):277-81.
    pubmed: 22338615
  7. Nigrovic PA, Mannion M, Prince FH, Zeft A, Rabinovich CE, van Rossum MA, Cortis E, Pardeo M, Miettunen PM, Janow G, Birmingham J, Eggebeen A, Janssen E, Shulman AI, Son MB, Hong S, Jones K, Ilowite NT, Cron RQ, Higgins GC. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.. Arthritis Rheum 2011 Feb;63(2):545-55.
    pubmed: 21280009doi: 10.1002/art.30128google scholar: lookup
  8. Auw Yang KG, Raijmakers NJ, van Arkel ER, Caron JJ, Rijk PC, Willems WJ, Zijl JA, Verbout AJ, Dhert WJ, Saris DB. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial.. Osteoarthritis Cartilage 2008 Apr;16(4):498-505.
    pubmed: 17825587doi: 10.1016/j.joca.2007.07.008google scholar: lookup
  9. Frisbie DD, Kawcak CE, Werpy NM, Park RD, McIlwraith CW. Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis.. Am J Vet Res 2007 Mar;68(3):290-6.
    pubmed: 17331019doi: 10.2460/ajvr.68.3.290google scholar: lookup
  10. Kraus VB, Birmingham J, Stabler TV, Feng S, Taylor DC, Moorman CT 3rd, Garrett WE, Toth AP. Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254).. Osteoarthritis Cartilage 2012 Apr;20(4):271-8.
    pubmed: 22273632doi: 10.1016/j.joca.2011.12.009google scholar: lookup
  11. 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
  12. Daheshia M, Yao JQ. The interleukin 1beta pathway in the pathogenesis of osteoarthritis.. J Rheumatol 2008 Dec;35(12):2306-12.
    pubmed: 18925684doi: 10.3899/jrheum.080346google scholar: lookup
  13. Pelletier JP, McCollum R, Cloutier JM, Martel-Pelletier J. Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process.. J Rheumatol Suppl 1995 Feb;43:109-14.
    pubmed: 7752112
  14. Saha N, Moldovan F, Tardif G, Pelletier JP, Cloutier JM, Martel-Pelletier J. Interleukin-1beta-converting enzyme/caspase-1 in human osteoarthritic tissues: localization and role in the maturation of interleukin-1beta and interleukin-18.. Arthritis Rheum 1999 Aug;42(8):1577-87.
    pubmed: 10446854doi: 10.1002/1529-0131(199908)42:8<1577::AID-ANR3>3.0.CO;2-Zgoogle scholar: lookup
  15. Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis.. J Rheumatol 1997 Feb;24(2):365-71.
    pubmed: 9034998
  16. Kubota E, Imamura H, Kubota T, Shibata T, Murakami K. Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint.. J Oral Maxillofac Surg 1997 Jan;55(1):20-7; discussion 27-8.
    pubmed: 8994464doi: 10.1016/s0278-2391(97)90438-9google scholar: lookup
  17. Loeser RF, Carlson CS, Del Carlo M, Cole A. Detection of nitrotyrosine in aging and osteoarthritic cartilage: Correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1.. Arthritis Rheum 2002 Sep;46(9):2349-57.
    pubmed: 12355482doi: 10.1002/art.10496google scholar: lookup
  18. Baltzer AW, Ostapczuk MS, Stosch D, Seidel F, Granrath M. A new treatment for hip osteoarthritis: clinical evidence for the efficacy of autologous conditioned serum.. Orthop Rev (Pavia) 2013 Jun 7;5(2):59-64.
    pmc: PMC3718237pubmed: 23888203doi: 10.4081/or.2013.e13google scholar: lookup
  19. 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
  20. Evans CH, Ghivizzani SC, Robbins PD. Getting arthritis gene therapy into the clinic.. Nat Rev Rheumatol 2011 Apr;7(4):244-9.
    pmc: PMC3460537pubmed: 21135882doi: 10.1038/nrrheum.2010.193google scholar: lookup
  21. Mease PJ, Wei N, Fudman EJ, Kivitz AJ, Schechtman J, Trapp RG, Hobbs KF, Greenwald M, Hou A, Bookbinder SA, Graham GE, Wiesenhutter CW, Willis L, Ruderman EM, Forstot JZ, Maricic MJ, Dao KH, Pritchard CH, Fiske DN, Burch FX, Prupas HM, Anklesaria P, Heald AE. Safety, tolerability, and clinical outcomes after intraarticular injection of a recombinant adeno-associated vector containing a tumor necrosis factor antagonist gene: results of a phase 1/2 Study.. J Rheumatol 2010 Apr;37(4):692-703.
    pubmed: 20032102doi: 10.3899/jrheum.090817google scholar: lookup
  22. 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
  23. Goodrich LR, Choi VW, Carbone BA, McIlwraith CW, Samulski RJ. Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors.. Hum Gene Ther 2009 Dec;20(12):1697-702.
    pmc: PMC2861962pubmed: 19642864doi: 10.1089/hum.2009.030google scholar: lookup
  24. Goodrich LR, Phillips JN, McIlwraith CW, Foti SB, Grieger JC, Gray SJ, Samulski RJ. Optimization of scAAVIL-1ra In Vitro and In Vivo to Deliver High Levels of Therapeutic Protein for Treatment of Osteoarthritis.. Mol Ther Nucleic Acids 2013 Feb 5;2(2):e70.
    pmc: PMC3586798pubmed: 23385523doi: 10.1038/mtna.2012.61google scholar: lookup
  25. 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
  26. Mason JB, Vandenberghe LH, Xiao R, Wilson JM, Richardson DW. Influence of serotype, cell type, tissue composition, and time after inoculation on gene expression in recombinant adeno-associated viral vector-transduced equine joint tissues.. Am J Vet Res 2012 Aug;73(8):1178-85.
    pubmed: 22849678doi: 10.2460/ajvr.73.8.1178google scholar: lookup
  27. Frisbie DD, Cross MW, McIlwraith CW. A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee.. Vet Comp Orthop Traumatol 2006;19(3):142-6.
    pubmed: 16971996
  28. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
    pmc: PMC3626203pubmed: 23610661doi: 10.1302/2046-3758.111.2000132google scholar: lookup
  29. Vandenberghe LH, Wilson JM. AAV as an immunogen.. Curr Gene Ther 2007 Oct;7(5):325-33.
    pubmed: 17979679doi: 10.2174/156652307782151416google scholar: lookup
  30. 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
  31. 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
  32. Cottard V, Valvason C, Falgarone G, Lutomski D, Boissier MC, Bessis N. Immune response against gene therapy vectors: influence of synovial fluid on adeno-associated virus mediated gene transfer to chondrocytes.. J Clin Immunol 2004 Mar;24(2):162-9.
    pubmed: 15024183doi: 10.1023/B:JOCI.0000019781.64421.5cgoogle scholar: lookup
  33. Boissier MC, Lemeiter D, Clavel C, Valvason C, Laroche L, Begue T, Bessis N. Synoviocyte infection with adeno-associated virus (AAV) is neutralized by human synovial fluid from arthritis patients and depends on AAV serotype.. Hum Gene Ther 2007 Jun;18(6):525-35.
    pubmed: 17532727doi: 10.1089/hum.2006.174google scholar: lookup
  34. Gouze E, Gouze JN, Palmer GD, Pilapil C, Evans CH, Ghivizzani SC. Transgene persistence and cell turnover in the diarthrodial joint: implications for gene therapy of chronic joint diseases.. Mol Ther 2007 Jun;15(6):1114-20.
    pubmed: 17440444doi: 10.1038/sj.mt.6300151google scholar: lookup
  35. Watanabe S, Imagawa T, Boivin GP, Gao G, Wilson JM, Hirsch R. Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium.. Mol Ther 2000 Aug;2(2):147-52.
    pubmed: 10947942doi: 10.1006/mthe.2000.0111google scholar: lookup
  36. Ulrich-Vinther M, Duch MR, Søballe K, O'Keefe RJ, Schwarz EM, Pedersen FS. In vivo gene delivery to articular chondrocytes mediated by an adeno-associated virus vector.. J Orthop Res 2004 Jul;22(4):726-34.
    pubmed: 15183427doi: 10.1016/j.orthres.2003.12.003google scholar: lookup
  37. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
    pmc: PMC3626203pubmed: 23610661doi: 10.1302/2046-3758.111.2000132google scholar: lookup
  38. 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
  39. Goodrich LR, Hidaka C, Robbins PD, Evans CH, Nixon AJ. Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model.. J Bone Joint Surg Br 2007 May;89(5):672-85.
    pubmed: 17540757doi: 10.1302/0301-620X.89B5.18343google scholar: lookup
  40. Morisset S, Frisbie DD, Robbins PD, Nixon AJ, McIlwraith CW. IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.. Clin Orthop Relat Res 2007 Sep;462:221-8.
    pubmed: 17534189doi: 10.1097/BLO.0b013e3180dca05fgoogle scholar: lookup
  41. Catterall JB, Stabler TV, Flannery CR, Kraus VB. Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254).. Arthritis Res Ther 2010;12(6):R229.
    pmc: PMC3046542pubmed: 21194441doi: 10.1186/ar3216google scholar: lookup
  42. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.. J Exp Med 2005 May 2;201(9):1479-86.
    pmc: PMC2213182pubmed: 15851489doi: 10.1084/jem.20050473google scholar: lookup
  43. Granowitz EV, Clark BD, Mancilla J, Dinarello CA. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor.. J Biol Chem 1991 Aug 5;266(22):14147-50.
    pubmed: 1830582
  44. Firestein GS, Berger AE, Tracey DE, Chosay JG, Chapman DL, Paine MM, Yu C, Zvaifler NJ. IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium.. J Immunol 1992 Aug 1;149(3):1054-62.
    pubmed: 1386092
  45. 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
  46. Arend WP. Interleukin-1 receptor antagonist.. Adv Immunol 1993;54:167-227.
    pubmed: 8379462doi: 10.1016/s0065-2776(08)60535-0google scholar: lookup
  47. Gabay C, Arend WP. Treatment of rheumatoid arthritis with IL-1 inhibitors.. Springer Semin Immunopathol 1998;20(1-2):229-46.
    pubmed: 9836379doi: 10.1007/BF00832009google scholar: lookup
  48. Bendele A, McAbee T, Woodward M, Scherrer J, Collins D, Frazier J, Chlipala E, McCabe D. Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type II collagen arthritis.. Pharm Res 1998 Oct;15(10):1557-61.
    pubmed: 9794498doi: 10.1023/a:1011903100188google scholar: lookup
  49. Rutgers M, Saris DB, Dhert WJ, Creemers LB. Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection.. Arthritis Res Ther 2010;12(3):R114.
    pmc: PMC2911907pubmed: 20537160doi: 10.1186/ar3050google scholar: lookup
  50. Bandara G, Mueller GM, Galea-Lauri J, Tindal MH, Georgescu HI, Suchanek MK, Hung GL, Glorioso JC, Robbins PD, Evans CH. Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer.. Proc Natl Acad Sci U S A 1993 Nov 15;90(22):10764-8.
    pmc: PMC47858pubmed: 8248169doi: 10.1073/pnas.90.22.10764google scholar: lookup
  51. Zhang X, Mao Z, Yu C. Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10.. J Orthop Res 2004 Jul;22(4):742-50.
    pubmed: 15183429doi: 10.1016/j.orthres.2003.12.007google scholar: lookup
  52. 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
  53. Wehling P, Reinecke J, Baltzer AW, Granrath M, Schulitz KP, Schultz C, Krauspe R, Whiteside TW, Elder E, Ghivizzani SC, Robbins PD, Evans CH. Clinical responses to gene therapy in joints of two subjects with rheumatoid arthritis.. Hum Gene Ther 2009 Feb;20(2):97-101.
    pmc: PMC2855248pubmed: 18986219doi: 10.1089/hum.2008.075google scholar: lookup
  54. Evans CH, Robbins PD, Ghivizzani SC, Wasko MC, Tomaino MM, Kang R, Muzzonigro TA, Vogt M, Elder EM, Whiteside TL, Watkins SC, Herndon JH. Gene transfer to human joints: progress toward a gene therapy of arthritis.. Proc Natl Acad Sci U S A 2005 Jun 14;102(24):8698-703.
    pmc: PMC1150836pubmed: 15939878doi: 10.1073/pnas.0502854102google scholar: lookup
  55. Mease PJ, Cohen S, Gaylis NB, Chubick A, Kaell AT, Greenwald M, Agarwal S, Yin M, Kelman A. Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial.. J Rheumatol 2010 May;37(5):917-27.
    pubmed: 20194448doi: 10.3899/jrheum.090442google scholar: lookup
  56. 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
  57. Gouze E, Pawliuk R, Gouze JN, Pilapil C, Fleet C, Palmer GD, Evans CH, Leboulch P, Ghivizzani SC. Lentiviral-mediated gene delivery to synovium: potent intra-articular expression with amplification by inflammation.. Mol Ther 2003 Apr;7(4):460-6.
    pubmed: 12727108doi: 10.1016/s1525-0016(03)00024-8google scholar: lookup
  58. Evans CH, Ghivizzani SC, Kang R, Muzzonigro T, Wasko MC, Herndon JH, Robbins PD. Gene therapy for rheumatic diseases.. Arthritis Rheum 1999 Jan;42(1):1-16.
    pubmed: 9920008doi: 10.1002/1529-0131(199901)42:1<1::AID-ANR1>3.0.CO;2-4google scholar: lookup
  59. Gray SJ, Matagne V, Bachaboina L, Yadav S, Ojeda SR, Samulski RJ. Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates.. Mol Ther 2011 Jun;19(6):1058-69.
    pmc: PMC3129805pubmed: 21487395doi: 10.1038/mt.2011.72google scholar: lookup

Citations

This article has been cited 17 times.
  1. 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 Sep 11;.
    doi: 10.1038/s41434-023-00420-2pubmed: 37696981google scholar: lookup
  2. Beaumont RE, Smith EJ, Zhou L, Marr N, Thorpe CT, Guest DJ. Exogenous interleukin-1 beta stimulation regulates equine tenocyte function and gene expression in three-dimensional culture which can be rescued by pharmacological inhibition of interleukin 1 receptor, but not nuclear factor kappa B, signaling.. Mol Cell Biochem 2023 Jun 14;.
    doi: 10.1007/s11010-023-04779-zpubmed: 37314623google 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. Kim AY, Duerr FM, Phillips JN, Samulski RJ, Grieger JC, Goodrich LR. Serotype-specific transduction of canine joint tissue explants and cultured monolayers by self-complementary adeno-associated viral vectors.. Gene Ther 2023 Apr;30(3-4):398-404.
    doi: 10.1038/s41434-022-00366-xpubmed: 36261499google scholar: lookup
  5. 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
  6. Watson-Levings RS, Palmer GD, Levings PP, Dacanay EA, Evans CH, Ghivizzani SC. Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.. Front Bioeng Biotechnol 2022;10:901317.
    doi: 10.3389/fbioe.2022.901317pubmed: 35837555google scholar: lookup
  7. Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W. Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses.. Animals (Basel) 2021 Nov 13;11(11).
    doi: 10.3390/ani11113247pubmed: 34827979google scholar: lookup
  8. 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
  9. Tendulkar G, Ehnert S, Sreekumar V, Chen T, Kaps HP, Golombek S, Wendel HP, Nüssler AK, Avci-Adali M. Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs-The Potential Role in Increasing Anabolic Response.. Int J Mol Sci 2019 Apr 6;20(7).
    doi: 10.3390/ijms20071716pubmed: 30959917google scholar: lookup
  10. Ball AN, Phillips JN, McIlwraith CW, Kawcak CE, Samulski RJ, Goodrich LR. 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.. J Orthop Res 2019 Jun;37(6):1310-1317.
    doi: 10.1002/jor.24209pubmed: 30578639google scholar: lookup
  11. 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. 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 2018 Jun;29(2):101-112.
    doi: 10.1089/humc.2017.143pubmed: 29869535google scholar: lookup
  12. Lykken EA, Shyng C, Edwards RJ, Rozenberg A, Gray SJ. Recent progress and considerations for AAV gene therapies targeting the central nervous system.. J Neurodev Disord 2018 May 18;10(1):16.
    doi: 10.1186/s11689-018-9234-0pubmed: 29776328google scholar: lookup
  13. Ball AN, Donahue SW, Wojda SJ, McIlwraith CW, Kawcak CE, Ehrhart N, Goodrich LR. The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.. J Orthop Res 2018 Jun;36(6):1559-1572.
    doi: 10.1002/jor.23845pubmed: 29280510google scholar: lookup
  14. Evans CH, Ghivizzani SC, Robbins PD. Gene Delivery to Joints by Intra-Articular Injection.. Hum Gene Ther 2018 Jan;29(1):2-14.
    doi: 10.1089/hum.2017.181pubmed: 29160173google scholar: lookup
  15. Bellavia D, Veronesi F, Carina V, Costa V, Raimondi L, De Luca A, Alessandro R, Fini M, Giavaresi G. Gene therapy for chondral and osteochondral regeneration: is the future now?. Cell Mol Life Sci 2018 Feb;75(4):649-667.
    doi: 10.1007/s00018-017-2637-3pubmed: 28864934google scholar: lookup
  16. Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes.. J Orthop Surg Res 2016 Feb 2;11:19.
    doi: 10.1186/s13018-016-0346-5pubmed: 26837951google scholar: lookup
  17. Aini H, Itaka K, Fujisawa A, Uchida H, Uchida S, Fukushima S, Kataoka K, Saito T, Chung UI, Ohba S. Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.. Sci Rep 2016 Jan 5;6:18743.
    doi: 10.1038/srep18743pubmed: 26728350google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.