%0 Journal Article
%T Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II
%A Bo Tang
%A David L Cullins
%A Jing Zhou
%A Janice A Zawaski
%A Hyelee Park
%A David D Brand
%A Karen A Hasty
%A M Waleed Gaber
%A John M Stuart
%A Andrew H Kang
%A Linda K Myers
%J Arthritis Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/ar3074
%X We engineered an adenoviral vector to contain the CB11 portion of recombinant type II collagen and used PCR to introduce point mutations at three sites within (CII124-402, 260A, 261B, 263D), (rCB11-A9) so that the resulting molecule contained the A9 sequence at the exact site of the wild-type sequence.We used this construct to target intra-articular tissues of mice and utilized the collagen-induced arthritis model to show that this treatment strategy provided a sustained, local therapy for individual arthritic joints, effective whether given to prevent arthritis or as a treatment. We also developed a novel system for in vivo bioimaging, using the firefly luciferase reporter gene to allow serial bioluminescence imaging to show that luciferase can be detected as late as 18 days post injection into the joint.Our therapy is unique in that we target synovial cells to ultimately shut down T cell-mediated inflammation. Its effectiveness is based on its ability to transform potential inflammatory T cells and/or bystander T cells into therapeutic (regulatory-like) T cells which secrete interleukin (IL)-4. We believe this approach has potential to effectively suppress RA with minimal side effects.Rheumatoid arthritis (RA) is a systemic disease with polyarticular manifestation of chronic inflammation in multiple articular joints, including the knees and small joints of the hands and feet. The current systemic anti-TNF-¦Á therapies ameliorate disease in 60% to 70% of RA patients [1]. However, biologics must be given systemically in relatively high dosages to achieve constant therapeutic levels in the joints, and significant side effects have been reported [2].Gene therapy may provide an effective alternative to drug delivery for the treatment of arthritis [3]. Although various strategies have been tested, those that target gene delivery to the synovial lining of joints have made the most experimental progress [3,4]. This strategy has shown efficacy in several experimental models
%U http://arthritis-research.com/content/12/4/R136