Generation of Gene-Engineered Chimeric DNA Molecules for Specific Therapy of Autoimmune Diseases

作者：Gesheva Vera; Szekeres Zsuzsanna; Mihaylova Nikolina; Dimitrova Iliyana; Nikolova Maria; Erdei Anna; Prechl Jozsef; Tchorbanov Andrey^*

来源：Human Gene Therapy Methods, 2012, 23(6): 357-365.

DOI：10.1089/hgtb.2012.051

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring, as a new DNA-based therapy of SLE, a chimeric DNA molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of an Fc gamma RIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The chimeric DNA molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. Intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase in IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile, and suppression of lupus nephritis.

• 出版日期2012-12