Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage

Henning Madry, Magali Cucchiarini, Ernest F. Terwilliger, Stephen B. Trippel

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. Using an rAAV vector carrying the Escherichia coli β-galactosidase gene (lacZ) under the control of the cytomegalovirus (CMV) immediate-early promoter/enhancer (rAAV-lacZ), transduction efficiency exceeded 70% for isolated normal human adult articular chondrocytes, and osteoarthritic human articular chondrocytes. These were comparable to the transduction efficiency obtained with neonatal bovine articular chondrocytes. Transduction of explant cultures of articular cartilage resulted in reporter gene expression within the tissue of all three cartilage types to a depth exceeding 450 μm, which remained present until 150 days. When rAAV-lacZ vectors were applied to femoral chondral defects and osteochondral defects in vivo in a rat knee model, reporter gene expression was achieved for at least 10 days after transduction. These data suggest that AAV-based vectors can efficiently transduce and stably express foreign genes in articular chondrocytes, including chondrocytes of normal and osteoarthritic human articular cartilage. The data further suggest that the same rAAV vectors are capable of transducing chondrocytes in situ within their native matrix to a depth sufficient to be of potential clinical significance. Finally, the data demonstrate that these rAAV vectors are capable of effectively delivering recombinant genes to chondral and osteochondral defects in vivo.

Original languageEnglish (US)
Pages (from-to)393-402
Number of pages10
JournalHuman Gene Therapy
Volume14
Issue number4
DOIs
StatePublished - Mar 1 2003

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Dependovirus
Articular Cartilage
Chondrocytes
Joints
Cartilage
Reporter Genes
Genes
Galactosidases
Gene Expression
Lac Operon
Thigh
Cytomegalovirus
Genetic Therapy
Knee
Escherichia coli

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. / Madry, Henning; Cucchiarini, Magali; Terwilliger, Ernest F.; Trippel, Stephen B.

In: Human Gene Therapy, Vol. 14, No. 4, 01.03.2003, p. 393-402.

Research output: Contribution to journalArticle

Madry, Henning ; Cucchiarini, Magali ; Terwilliger, Ernest F. ; Trippel, Stephen B. / Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. In: Human Gene Therapy. 2003 ; Vol. 14, No. 4. pp. 393-402.
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