Chronic respiratory diseases are a significant health problem requiring novel approaches to both complement
existing therapies and provide breakthrough medicines. Recent clinical advances in understanding the behavior of inhaled
oligonucleotides provide the impetus for application of this technology to microRNA therapeutics. MicroRNAs are
evolutionarily conserved small regulatory RNA molecules involved in tuning gene networks controlling biological and
pathological processes. Deletion or overexpression of microRNAs results in phenotypic changes in animal models of
disease such as cancer, fibrosis, diabetes, and inflammation. Inhibition of microRNAs in preclinical models of asthma,
cystic fibrosis, and idiopathic pulmonary fibrosis has shown therapeutic promise. In animals, inhibitors of microRNAs
directly delivered to the airway at doses suitable for nebulizers or hand-held inhalers up-regulate expression of cohorts of
genes containing complementary “seed” sequences for specific and directed microRNA binding within their mRNA
untranslated regions. These observations suggest the opportunity to exploit intervention in microRNA biology to create
new therapies for chronic pulmonary disorders.
Keywords: Inhaled anti-miRs, microRNA, pulmonary inflammation, regulatory gene networks.
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