FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Hum Gene Ther / Ex vivo serotype-specific transduction of equine joint tissu...
Human gene therapy2009; 20(12); 1697-1702; doi: 10.1089/hum.2009.030

Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors.

Abstract: Cell transplantation for the treatment of joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in joint tissue containing chondrocytes and synoviocytes isolated from equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of joint-related diseases.
Get Full Text
Publication Date: 2009-08-01 PubMed ID: 19642864PubMed Central: PMC2861962DOI: 10.1089/hum.2009.030Google 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 research paper describes a study involving the use of certain types of viruses to modify cells ex vivo (outside the body), potentially improving treatment of joint diseases. Particularly, the study examined the effectiveness of various serotypes of adeno-associated virus (AAV) in modifying cells from horse joint tissue.

Objective of the Study

  • The primary objective of this study was to analyze the ability of various serotypes (or variations) of adeno-associated virus (AAV) to modify cells found in equine (horse) joint tissue outside of the body. This process is known as ex vivo serotype-specific transduction.

Methodology

  • The researchers tested a set of self-complementary AAV serotypes (1-6 and 8) on joint tissue containing chondrocytes and synoviocytes. These are types of cells found in joints that play a role in joint health and disease.
  • The process of genetic modification was conducted outside the living body, thus making it an ‘ex vivo’ process.
  • The effectiveness of the serotypes was determined by their efficiency in cell transduction, or the ability to introduce new genes into cells.

Results and Findings

  • The study pointed out that certain AAV serotypes were superior in terms of their transduction efficiency. In the case of chondrocytes, serotypes 6 and 2 showed high efficiency, while for synoviocytes, serotypes 3 and 2 were superior.
  • Unlike treatments involving adenoviral vectors, using AAV vectors did not lead to an increase in inflammatory markers, like matrix metalloproteinases and aggrecanase.
  • The research also showed that ex vivo transduction of joint tissue can result in high transgene protein levels over time. This finding suggests that cell transplantation might be improved through cell modification via AAV vectors, making it a potentially effective treatment for joint-related diseases.

Cite This Article

APA
Goodrich LR, Choi VW, Carbone BA, McIlwraith CW, Samulski RJ. (2009). Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors. Hum Gene Ther, 20(12), 1697-1702. https://doi.org/10.1089/hum.2009.030

Publication

Human gene therapy
ISSN: 1557-7422
NlmUniqueID: 9008950
Country: United States
Language: English
Volume: 20
Issue: 12
Pages: 1697-1702

Researcher Affiliations

Goodrich, L R
  • Orthopaedic Research Center, College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA.
Choi, V W
    Carbone, B A Duda
      McIlwraith, C W
        Samulski, R J

          MeSH Terms

          • Animals
          • Chondrocytes / cytology
          • Chondrocytes / transplantation
          • Dependovirus / classification
          • Dependovirus / genetics
          • Genetic Vectors / classification
          • Genetic Vectors / genetics
          • Horses
          • Serotyping
          • Synovial Membrane / cytology
          • Synovial Membrane / transplantation
          • Transduction, Genetic / methods

          Grant Funding

          • 1K08AR054903-01A2 / NIAMS NIH HHS

          References

          This article includes 40 references
          1. Adriaansen J, Tas SW, Klarenbeek PL, Bakker AC, Apparailly F, Firestein GS, Jorgensen C, Vervoordeldonk MJ, Tak PP. Enhanced gene transfer to arthritic joints using adeno-associated virus type 5: implications for intra-articular gene therapy.. Ann Rheum Dis 2005 Dec;64(12):1677-84.
            pmc: PMC1755308pubmed: 15878906doi: 10.1136/ard.2004.035063google scholar: lookup
          2. Bartlett JS, Wilcher R, Samulski RJ. Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors.. J Virol 2000 Mar;74(6):2777-85.
            pmc: PMC111768pubmed: 10684294doi: 10.1128/jvi.74.6.2777-2785.2000google scholar: lookup
          3. Brower-Toland BD, Saxer RA, Goodrich LR, Mi Z, Robbins PD, Evans CH, Nixon AJ. Direct adenovirus-mediated insulin-like growth factor I gene transfer enhances transplant chondrocyte function.. Hum Gene Ther 2001 Jan 20;12(2):117-29.
            pubmed: 11177549doi: 10.1089/104303401750061186google scholar: lookup
          4. Choi VW, McCarty DM, Samulski RJ. AAV hybrid serotypes: improved vectors for gene delivery.. Curr Gene Ther 2005 Jun;5(3):299-310.
            pmc: PMC1462937pubmed: 15975007doi: 10.2174/1566523054064968google scholar: lookup
          5. Cucchiarini M, Madry H. Gene therapy for cartilage defects.. J Gene Med 2005 Dec;7(12):1495-509.
            pubmed: 16142829doi: 10.1002/jgm.824google scholar: lookup
          6. Dai J, Rabie AB. Direct AAV-mediated gene delivery to the temporomandibular joint.. Front Biosci 2007 Jan 1;12:2212-20.
            pubmed: 17127458doi: 10.2741/2224google scholar: lookup
          7. Dai J, Rabie AB. Recombinant adeno-associated virus vector hybrids efficiently target different skeletal cells.. Front Biosci 2007 May 1;12:4280-7.
            pubmed: 17485374doi: 10.2741/2387google scholar: lookup
          8. Duan D, Yue Y, Yan Z, Yang J, Engelhardt JF. Endosomal processing limits gene transfer to polarized airway epithelia by adeno-associated virus.. J Clin Invest 2000 Jun;105(11):1573-87.
            pmc: PMC300848pubmed: 10841516doi: 10.1172/jci8317google scholar: lookup
          9. Evans CH. Gene therapies for osteoarthritis.. Curr Rheumatol Rep 2004 Feb;6(1):31-40.
            pubmed: 14713400doi: 10.1007/s11926-004-0081-5google scholar: lookup
          10. Evans CH, Robbins PD. Gene therapy for arthritis.. In: Wolff J.A., editor. Gene Therapeutics: Methods and Applications of Direct Gene Transfer. Birkhauser; Cambridge: 1994. pp. 320–343.
          11. Evans CH, Gouze JN, Gouze E, Robbins PD, Ghivizzani SC. Osteoarthritis gene therapy.. Gene Ther 2004 Feb;11(4):379-89.
            pubmed: 14724685doi: 10.1038/sj.gt.3302196google scholar: lookup
          12. Fortier LA, Nixon AJ. New surgical treatments for osteochondritis dissecans and subchondral bone cysts.. Vet Clin North Am Equine Pract 2005 Dec;21(3):673-90, vii.
            pubmed: 16297727doi: 10.1016/j.cveq.2005.07.005google scholar: lookup
          13. Gao G, Vandenberghe LH, Wilson JM. New recombinant serotypes of AAV vectors.. Curr Gene Ther 2005 Jun;5(3):285-97.
            pubmed: 15975006doi: 10.2174/1566523054065057google scholar: lookup
          14. Ghivizzani SC, Lechman ER, Kang R, Tio C, Kolls J, Evans CH, Robbins PD. Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor alpha soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects.. Proc Natl Acad Sci U S A 1998 Apr 14;95(8):4613-8.
            pmc: PMC22538pubmed: 9539786doi: 10.1073/pnas.95.8.4613google scholar: lookup
          15. 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
          16. Goodrich LR, Nixon AJ, Hidaka C, Robbins PD, Evans CH. Enhanced early repair and cell survival in cartilage defects implanted with chondrocytes over expressing insulin-like growth factor-I.. Vet. Surg. 2005;34:E8.
          17. Goodrich LR, Brower-Toland BD, Warnick L, Robbins PD, Evans CH, Nixon AJ. Direct adenovirus-mediated IGF-I gene transduction of synovium induces persisting synovial fluid IGF-I ligand elevations.. Gene Ther 2006 Sep;13(17):1253-62.
            pubmed: 16708081doi: 10.1038/sj.gt.3302757google scholar: lookup
          18. 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
          19. Gouze E, Pawliuk R, Pilapil C, Gouze JN, Fleet C, Palmer GD, Evans CH, Leboulch P, Ghivizzani SC. In vivo gene delivery to synovium by lentiviral vectors.. Mol Ther 2002 Apr;5(4):397-404.
            pubmed: 11945066doi: 10.1006/mthe.2002.0562google scholar: lookup
          20. 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
          21. Gouze JN, Gouze E, Palmer GD, Kaneto H, Ghivizzani SC, Grodzinsky AJ, Evans CH. Adenovirus-mediated gene transfer of glutamine: fructose-6-phosphate amidotransferase antagonizes the effects of interleukin-1beta on rat chondrocytes.. Osteoarthritis Cartilage 2004 Mar;12(3):217-24.
            pubmed: 14972338doi: 10.1016/j.joca.2003.11.002google scholar: lookup
          22. Grimm D, Kay MA. From virus evolution to vector revolution: use of naturally occurring serotypes of adeno-associated virus (AAV) as novel vectors for human gene therapy.. Curr Gene Ther 2003 Aug;3(4):281-304.
            pubmed: 12871018doi: 10.2174/1566523034578285google scholar: lookup
          23. Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H, Lust G. Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects.. J Orthop Res 1994 Jul;12(4):485-97.
            pubmed: 8064479doi: 10.1002/jor.1100120405google scholar: lookup
          24. Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ. Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7.. J Orthop Res 2003 Jul;21(4):573-83.
            pubmed: 12798054doi: 10.1016/s0736-0266(02)00264-4google scholar: lookup
          25. Ishiguro N, Kojima T. [Role of aggrecanase and MMP in cartilage degradation].. Clin Calcium 2004 Jul;14(7):38-44.
            pubmed: 15577074
          26. Kafienah W, Al-Fayez F, Hollander AP, Barker MD. Inhibition of cartilage degradation: a combined tissue engineering and gene therapy approach.. Arthritis Rheum 2003 Mar;48(3):709-18.
            pubmed: 12632424doi: 10.1002/art.10842google scholar: lookup
          27. Madry H, Cucchiarini M, Terwilliger EF, Trippel SB. Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage.. Hum Gene Ther 2003 Mar 1;14(4):393-402.
            pubmed: 12659680doi: 10.1089/104303403321208998google scholar: lookup
          28. Madry H, Kaul G, Cucchiarini M, Stein U, Zurakowski D, Remberger K, Menger MD, Kohn D, Trippel SB. Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I).. Gene Ther 2005 Aug;12(15):1171-9.
            pubmed: 15815701doi: 10.1038/sj.gt.3302515google scholar: lookup
          29. Marlovits S, Kutscha-Lissberg F, Aldrian S, Resinger C, Singer P, Zeller P, Vécsei V. [Autologous chondrocyte transplantation for the treatment of articular cartilage defects inf the knee joint. Techniques and results].. Radiologe 2004 Aug;44(8):763-72.
            pubmed: 15338139doi: 10.1007/s00117-004-1082-0google scholar: lookup
          30. 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
          31. Nixon AJ, Lust G, Vernier-Singer M. Isolation, propagation, and cryopreservation of equine articular chondrocytes.. Am J Vet Res 1992 Dec;53(12):2364-70.
            pubmed: 1476323
          32. Rabinowitz JE, Rolling F, Li C, Conrath H, Xiao W, Xiao X, Samulski RJ. Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity.. J Virol 2002 Jan;76(2):791-801.
            pmc: PMC136844pubmed: 11752169doi: 10.1128/jvi.76.2.791-801.2002google scholar: lookup
          33. Rivière C, Danos O, Douar AM. Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice.. Gene Ther 2006 Sep;13(17):1300-8.
            pubmed: 16688207doi: 10.1038/sj.gt.3302766google scholar: lookup
          34. Sams AE, Nixon AJ. Studies of chondrocyte laden collagen scaffolds for resurfacing extensive equine articular cartilage defects.. MS thesis. Cornell University; Ithaca, New York: 1993.
          35. Sanlioglu S, Monick MM, Luleci G, Hunninghake GW, Engelhardt JF. Rate limiting steps of AAV transduction and implications for human gene therapy.. Curr Gene Ther 2001 Jul;1(2):137-47.
            pubmed: 12108951doi: 10.2174/1566523013348788google scholar: lookup
          36. Saxer RA, Bent SJ, Brower-Toland BD, Mi Z, Robbins PD, Evans CH, Nixon AJ. Gene mediated insulin-like growth factor-I delivery to the synovium.. J Orthop Res 2001 Sep;19(5):759-67.
            pubmed: 11562119doi: 10.1016/s0736-0266(00)00077-2google scholar: lookup
          37. Schmidt M, Voutetakis A, Afione S, Zheng C, Mandikian D, Chiorini JA. Adeno-associated virus type 12 (AAV12): a novel AAV serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity.. J Virol 2008 Feb;82(3):1399-406.
            pmc: PMC2224443pubmed: 18045941doi: 10.1128/jvi.02012-07google scholar: lookup
          38. Ulrich-Vinther M. Gene therapy methods in bone and joint disorders. Evaluation of the adeno-associated virus vector in experimental models of articular cartilage disorders, periprosthetic osteolysis and bone healing.. Acta Orthop Suppl 2007 Apr;78(325):1-64.
            pubmed: 17427340
          39. Ulrich-Vinther M, Stengaard C, Schwarz EM, Goldring MB, Soballe K. Adeno-associated vector mediated gene transfer of transforming growth factor-beta1 to normal and osteoarthritic human chondrocytes stimulates cartilage anabolism.. Eur Cell Mater 2005 Nov 14;10:40-50.
            pubmed: 16284937doi: 10.22203/ecm.v010a05google scholar: lookup
          40. Wu Z, Asokan A, Samulski RJ. Adeno-associated virus serotypes: vector toolkit for human gene therapy.. Mol Ther 2006 Sep;14(3):316-27.
            pubmed: 16824801doi: 10.1016/j.ymthe.2006.05.009google scholar: lookup

          Citations

          This article has been cited 22 times.
          1. Nagelli CV, Evans CH, De La Vega RE. Viral Gene Delivery in Chondrocytes.. Methods Mol Biol 2023;2598:289-300.
            doi: 10.1007/978-1-0716-2839-3_20pubmed: 36355299google scholar: lookup
          2. 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
          3. 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
          4. Yoon DS, Lee KM, Cho S, Ko EA, Kim J, Jung S, Shim JH, Gao G, Park KH, Lee JW. Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage.. Int J Med Sci 2021;18(15):3353-3360.
            doi: 10.7150/ijms.56760pubmed: 34522160google scholar: lookup
          5. 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
          6. Arrigoni P, Ruprecht JC, Chasse DAD, Glass KA, Andress B, Guilak F, Weinberg JB, McNulty AL. Optimization of Meniscus Cell Transduction Using Lentivirus and Adeno-Associated Virus for Gene Editing and Tissue Engineering Applications.. Cartilage 2021 Dec;13(2_suppl):1602S-1607S.
            doi: 10.1177/1947603519880321pubmed: 31609141google scholar: lookup
          7. 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
          8. Ortved KF, Austin BS, Scimeca MS, Nixon AJ. RNA Interference Mediated Interleukin-1β Silencing in Inflamed Chondrocytes Decreases Target and Downstream Catabolic Responses.. Arthritis 2016;2016:3484961.
            doi: 10.1155/2016/3484961pubmed: 27073697google scholar: lookup
          9. Malda J, McIlwraith CW. Current Trends in Cartilage Science: An Impression from the ICRS World Conference 2012.. Cartilage 2013 Oct;4(4):273-80.
            doi: 10.1177/1947603513479606pubmed: 26069672google 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.
            doi: 10.1038/gt.2015.21pubmed: 25902762google scholar: lookup
          11. 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.
            doi: 10.1089/hum.2014.050pubmed: 25705927google scholar: lookup
          12. Cucchiarini M, Madry H. Use of tissue engineering strategies to repair joint tissues in osteoarthritis: viral gene transfer approaches.. Curr Rheumatol Rep 2014 Oct;16(10):449.
            doi: 10.1007/s11926-014-0449-0pubmed: 25182677google scholar: lookup
          13. Hemphill DD, McIlwraith CW, Samulski RJ, Goodrich LR. Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers.. Sci Rep 2014 Jul 29;4:5861.
            doi: 10.1038/srep05861pubmed: 25069854google scholar: lookup
          14. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
            doi: 10.1302/2046-3758.111.2000132pubmed: 23610661google scholar: lookup
          15. 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.
            doi: 10.1038/mtna.2012.61pubmed: 23385523google scholar: lookup
          16. Evans CH, Ghivizzani SC, Robbins PD. Arthritis gene therapy and its tortuous path into the clinic.. Transl Res 2013 Apr;161(4):205-16.
            doi: 10.1016/j.trsl.2013.01.002pubmed: 23369825google scholar: lookup
          17. 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.
            doi: 10.1038/gt.2012.81pubmed: 23151520google scholar: lookup
          18. 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.
            doi: 10.1155/2012/735472pubmed: 22288012google scholar: lookup
          19. Aalbers CJ, Tak PP, Vervoordeldonk MJ. Advancements in adeno-associated viral gene therapy approaches: exploring a new horizon.. F1000 Med Rep 2011;3:17.
            doi: 10.3410/M3-17pubmed: 21941595google scholar: lookup
          20. Raj D, Davidoff AM, Nathwani AC. Self-complementary adeno-associated viral vectors for gene therapy of hemophilia B: progress and challenges.. Expert Rev Hematol 2011 Oct;4(5):539-49.
            doi: 10.1586/ehm.11.48pubmed: 21939421google scholar: lookup
          21. Payne KA, Lee HH, Haleem AM, Martins C, Yuan Z, Qiao C, Xiao X, Chu CR. Single intra-articular injection of adeno-associated virus results in stable and controllable in vivo transgene expression in normal rat knees.. Osteoarthritis Cartilage 2011 Aug;19(8):1058-65.
            doi: 10.1016/j.joca.2011.04.009pubmed: 21571082google scholar: lookup
          22. Alaee F, Sugiyama O, Virk MS, Tang Y, Wang B, Lieberman JR. In vitro evaluation of a double-stranded self-complementary adeno-associated virus type2 vector in bone marrow stromal cells for bone healing.. Genet Vaccines Ther 2011 Feb 27;9:4.
            doi: 10.1186/1479-0556-9-4pubmed: 21352585google scholar: lookup
          Subscribe to our newsletter
          Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.