PT  - JOURNAL ARTICLE
AU  - Perlman, Harris
AU  - Liu, Hongtao
AU  - Georganas, Constantinos
AU  - Woods, James M
AU  - Amin, M Asif
AU  - Koch, Alisa E
AU  - Wickham, Thomas
AU  - Kovesdi, Imre
AU  - Mano, Toshiaki
AU  - Walsh, Kenneth
AU  - Pope, Richard M
TI  - Modifications in adenoviral coat fiber proteins and transcriptional regulatory sequences enhance transgene expression.
DP  - 2002 Aug 01
TA  - The Journal of Rheumatology
PG  - 1593--1600
VI  - 29
IP  - 8
4099  - http://www.jrheum.org/content/29/8/1593.short
4100  - http://www.jrheum.org/content/29/8/1593.full
SO  - J Rheumatol2002 Aug 01; 29
AB  - OBJECTIVE: To characterize the adenoviral properties required to enhance intracellular transgene expression for gene therapy. METHODS: Primary human fibroblasts and macrophages were infected with standard replication-defective adenoviruses, adenoviral vectors containing modified fiber coat proteins expressing Arg-Gly-Asp (RGD) or heparin sulfate binding moieties, or a tetracycline-regulatable transgene transcription system. Each of these vectors expressed the beta-galactosidase gene (beta-Gal), which was quantified by flow cytometry. Ankle joints from rats with adjuvant induced arthritis were transduced intraarticularly with each of the vectors and B-Gal expression was quantified by flow cytometry. RESULTS: Primary human fibroblasts and macrophages displayed marked increases in transgene expression from both modified fiber protein vectors and from the tetracycline-regulatable vector, compared to an unmodified vector expressing the transgene from the cytomegalovirus promoter/enhancer. In the rat model, the modified fiber protein vectors and the tetracycline-regulatable vector system also displayed increased transgene expression in inflamed rat joints. CONCLUSION: Adenovirus attachment and uptake by cells and promoter strength limit transgene expression from conventional adenoviral vectors in models of rheumatoid arthritis.