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BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome (pSS). ΔBAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7 RNA was reengineered to deliver antisense sequences targeting BAFF splice regions. A major decrease of BAFF messenger RNA (mRNA) and protein secretion, concomitantly with the increase of ΔBAFF mRNA, was observed in vitro. In vivo, SG retrograd instillation of nonobese diabetic mice by the modified U7 cloned into an adeno-associated virus vector significantly decreased BAFF protein expression and lymphocytic infiltrates and improved salivary flow. This study offers a rationale for localized therapeutic BAFF inhibition in pSS and represents a proof of concept of the interest of exon skipping in autoimmune diseases.

Original publication




Journal article


Molecular therapy : the journal of the American Society of Gene Therapy

Publication Date





821 - 827


1] Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands [2] Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.


B-Lymphocytes, Animals, Mice, Inbred NOD, Humans, Mice, Dependovirus, Sjogren's Syndrome, RNA, Messenger, RNA, Small Nuclear, Lymphocyte Activation, RNA Splicing, Exons, B-Cell Activating Factor