Gene therapy for autoimmune diseases: quo vadis ?

Key Points Common pathological processes in autoimmune diseases, such as the apoptosis of cells, and the production and action of pro-inflammatory cytokines, can be targeted by gene therapy. Tissue repair can also be mediated by gene therapy: for example, by inducing the differentiation of liver cells to express insulin. There have been many advances in non-immunogenic gene-delivery systems for the treatment of autoimmune diseases, including the engineering of latent cytokines. Protein therapy has several advantages compared with gene therapy, and the two types of therapy show pharmacokinetic differences. Advances in transcription-regulated vector systems are important for the therapy of chronic relapsing–remitting conditions, such as multiple sclerosis. Advances in ex vivo cell engineering have allowed researchers to modify cell–cell interactions and to target cells to specific tissues. Biological therapies using antibodies and cytokines are becoming widespread for the treatment of chronic inflammatory autoimmune diseases. However, these treatments have several limitations — such as expense, the need for repeated injections and unwanted side-effects — that can be overcome by genetic delivery. This review summarizes the ingenuity, sophistication and variety of gene-therapy approaches that have been taken in the design of therapeutic molecules and vectors, the engineering of cells and the regulation of gene expression for the targeting of disease outcome. We focus our attention on multiple sclerosis, type 1 diabetes and rheumatoid arthritis.