Treatment of allergic asthma by targeting transcription factors using nucleic-acid based technologies.
There is considerable evidence that T-helper 2 (Th2) cells play a central role in the pathogenesis of allergic diseases such as bronchial asthma, hay fever or food allergy. The differentiation of naïve T cells into Th2 cells producing a specific pattern of cytokines is tightly controlled and regulated by transcription factors. Thus down-regulation of mRNA-levels of a single transcription factor leads to a "knock-down" of several mediators simultaneously, representing an advantage compared to earlier approaches involving down-regulation of one intercellular inflammatory mediator, which is unlikely to influence all pathophysiological aspects of the disease. We review the impact of specific and master transcription factors involved in Th2 cell commitment and evaluate approaches for the down-regulation of these proteins by degradation of their mRNA using nucleic-acid based technologies including antisense oligonucleotides, ribozymes, DNAzymes, decoys oligonucleotides and RNA interference.
Sel
Serdar
S
Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps University Marburg, Baldingerstrasse, D-35033 Marburg, Germany. sel@med.uni-marburg.de
Henke
Wolfgang
W
Dietrich
Alexander
A
Herz
Udo
U
Renz
Harald
H
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009696:Nucleic Acids / Q000235:genetics* / Q000627:therapeutic use; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D000485:Allergens; D018927:Anti-Asthmatic Agents; D009696:Nucleic Acids; D014157:Transcription Factors