Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis.

Introduction: Proof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis (RA). For the treatment of RA patients, we engineered a recombinant adeno-associated serotype 5 vector (rAAV5) encoding human (h)IFN-β under control of a nuclear factor κB promoter (ART-I02).

Methods: The potency of ART-I02 in vitro as well as biodistribution in vivo in arthritic animals was evaluated to characterize the vector prior to clinical application.

Bone marrow-derived macrophages incorporate into the endothelium and influence vascular and renal function after irradiation.

Purpose: We recently demonstrated that endoglin, an ancillary transforming growth factor beta (TGF-β) receptor, modulates vascular damage and fibrosis formation and influences renal function after kidney irradiation. We also suggested that this was partially accomplished by endoglin-mediated regulation of cytokine production in macrophages. Endoglin is expressed on both endothelial cells and on activated macrophages.