New Biological Approaches in Asthma: DNA-Based Therapy

Li-Chieh      Wang; Jyh-Hong      Lee; Yao-Hsu      Yang; Yu-Tsan      Lin; Bor-Luen      Chiang

Abstract

Asthma is characterized by airway inflammation, bronchial hyper-responsiveness, and reversible airway obstruction. Medications for asthma include corticosteroids, β2-adrenergic receptor agonists, chromones, methylxanthines, and leukotriene modifiers. Despite these advances in therapy, many symptoms are not well controlled. Since asthma is a chronic airway inflammation with a bias towards a type 2 T helper (Th2) cell response, some new approaches are targeted towards the Th2 inflammation pathway. These include anti-IgE therapy, anti-Th2 cytokine therapy, and therapies aiming at increasing Th1 cytokines. This article will focus on DNA-based therapy, a novel therapeutic strategy for asthma. Immunostimulatory gene therapy using CpG oligodeoxynucleotides with central deoxycytidyl-deoxyguanosine (CpG) dinucleotide, in which the cytosine nucleobase is unmethylated, can stimulate the innate immunity and augment Th1 response. With DNA gene therapy, genes can be introduced to target Th1 cytokines or other mediators in the airway in order to counteract Th2 inflammation in asthma. Also, antisense oligonucleotides can target mRNA species of interest in asthma. Through these therapies, we can expect long-lasting effects, better control of symptoms, and reducing medication in the future.

Keywords: Asthma, Th1/Th2, cytokine, CpG, gene therapy, antisense oligonucleotides

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