Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis.

:To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/0-) and a second-generation HSV vector derivative (T/0-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a soluble TNF receptor or IL-1 receptor antagonist transgene cassette. A rabbit synovial-fibroblast line in culture, infected by either vector enabled high-level expression of the transgene product. However, following a single intra-articular injection of the vectors into rabbit knee joints, only the second-generation, HSV T/0- vector expressed detectable levels of soluble TNFR in synovial fluid. Synovial lavage fluid from inoculated joints con- tained up to 12 ng/ml of soluble receptor that persisted at detectable, but reduced levels for at least 7 days. When tested in an experimental model of arthritis generated by intra-articular overexpression of interleukin-1beta using retrovirus transduced synovial cells, the HSV T/0- vector expressing the interleukin-1 receptor antagonist was found to inhibit leukocytosis and synovitis significantly. The improved levels and duration of intra-articular transgene expression achieved via HSV-mediated gene delivery suggest that an HSV vector system could be used for therapeutic applications in patients with rheumatoid arthritis (RA) and other joint-related inflammatory diseases.

Oligino T ，Ghivizzani S ，Wolfe D ，Lechman E ，Krisky D ，Mi Z ，Evans C ，Robbins P ，Glorioso J ... -  《GENE THERAPY》

Suppression of experimental osteoarthritis by adenovirus-mediated double gene transfer.

Wang HJ ，Yu CL ，Kishi H ，Motoki K ，Mao ZB ，Muraguchi A ... -  《CHINESE MEDICAL JOURNAL》

Adenoviral delivery of IL-1 receptor antagonist abrogates disease activity during the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice.

Hur W ，Cho ML ，Yoon SK ，Kim SY ，Ju JH ，Jhun JY ，Heo SB ，Moon YM ，Min SY ，Park SH ，Kim HY ... -  《IMMUNOLOGY LETTERS》

Interleukin-1 receptor antagonist gene therapy for arthritis.

Krishnan BR 《-》

Ex vivo gene delivery of IL-1Ra and soluble TNF receptor confers a distal synergistic therapeutic effect in antigen-induced arthritis.

Kim SH ，Lechman ER ，Kim S ，Nash J ，Oligino TJ ，Robbins PD ... -  《MOLECULAR THERAPY》