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Development of lentiviral vectors for gene therapy of arthritis

Arthritis Research
Springer (Biomed Central Ltd.)
Publication Date
DOI: 10.1186/ar351
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  • Medicine


abstracts.qxd P1 Adeno-associated virus preferentially transduces human compared to mouse synovium K Jennings, S Katakura, H Burstein, G Gao, JM Wilson, R Hirsch Division of Rheumatology, Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Institute for Human Gene Therapy, University of Pennsylvania Health System, Philadelphia, PA 19104, USA; Targeted Genetics Corp, Seattle, WA 98101, USA There is increasing interest in adeno-associated virus (AAV) vectors for a wide variety of gene therapy applications. AAV is a nonpathogenic human parvovirus that can mediate long-term trans- duction of a number of cell types without provoking a significant immune response. These properties make AAV especially attrac- tive for use in gene therapy of rheumatoid arthritis (RA), a chronic inflammatory disease. To investigate the potential of AAV in gene therapy of arthritis, the ability of AAV to infect synovium in vitro and in vivo was tested. Three human RA synovial fibroblast cell lines and two murine (one DBA/1J and one DBA1J×C3H F1) synovial fibroblast cell lines were used to test AAV transduction in vitro. The cell lines (2 × 105 cells) were infected with 104 particles/cell of a murine IL-10-encoding vector (AAV-mIL-10) alone or with the addi- tion of a low titer (100 particles/cell) of an E1-, E3-deleted recom- binant adenovirus to provide E4orf6 activity to enhance second-strand synthesis. The supernatants were harvested from the wells at various time points and assayed for mIL-10 expression by ELISA. Both human synovial cell lines infected with AAV alone demonstrated low-level transgene expression throughout the course of the study. However, by day 10, all human cultures coin- fected with adenovirus showed a 16- to 56-fold increase in mIL-10 compared to cultures infected with AAV-mIL10 alone. By day 30, a 31- to 135-fold increase was observed. No such increase was observed in any of the mouse cell lines. To determine the AAV transduction efficiency for synovium in vivo, human RA syno

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