In vivo gene delivery to articular chondrocytes mediated by an adeno-associated virus vector

Michael Ulrich-Vinther, M. R. Duch, K. Søballe, R. J. O'Keefe, E. M. Schwarz, F. S. Pedersen

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Purposes. (1) To investigate the efficiency of direct in vivo adeno-associated virus (AAV) vector-mediated gene transduction to chondrocytes in relation to normal and injured articular cartilage. (2) To evaluate the effects of ultra-violet light-activated gene transduction (LAGT) in chondrocytes in vivo. (3) To determine dissemination of active rAAV vector after intra-articular administration. Methods. Rabbit knees with either normal or injured cartilage received an intra-articular injection with 1.5 × 1012 infectious rAAV-eGFP particles. The right knees received rAAV-eGFP alone, whereas the left knees were given LAGT-treatment. The transduction efficiencies were determined at 1 and 3 weeks after infection by fluorescence-activated cell scanning. The occurrence of active shedding was monitored in serum and various tissues. Results. After 1 week, 7% of the chondrocytes in normal cartilage were transduced by direct rAAV transduction technique. Chondrocytes in cartilage defects demonstrated higher transduction rates compared to chondrocytes in normal cartilage. LAGT increased the cellular eGFP expression in the internal zones to 12%, but did not have any effect in the external zones in defects. Finally, infectious particles were not detected in either serum or tissue samples. Conclusions. Direct rAAV-mediated gene transfer in vivo to articular chondrocytes is possible. LAGT improves rAAV transduction of chondrocytes in vivo but appears to have a very limited range of effect induction. Expression of eGFP was not determined in other tissues than synovium and cartilage in the treated joints.

Original languageEnglish
Pages (from-to)726-734
Number of pages9
JournalJournal of Orthopaedic Research
Volume22
Issue number4
DOIs
StatePublished - Jun 23 2004
Externally publishedYes

Keywords

  • Basic fibroblast growth factor
  • Chondrogenesis
  • Growth hormone
  • Periosteum
  • Serum-free media
  • Transforming growth factor beta

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