From Obstruction To Destruction

A Discussion on Respiratory Lung Diseases.
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According to a report by the World Health Organization, deaths due to pulmonary diseases in India were on the rise accounting for 11 percent of the total deaths. India bears a 32 percent global burden of respiratory diseases. COPD and Asthma were held responsible for being the reason behind 75.6% and 20.0% of the chronic respiratory disease.

The term lung disease refers to many disorders affecting the lungs, such as asthma, COPD, infections like influenza, pneumonia and tuberculosis, lung cancer, and many other breathing problems. Some lung diseases can lead to respiratory failure. Chronic Inflammatory lung disease causes obstructive airflow from the lungs. Asthma is a chronic inflammatory disease. Even though current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients. Increased expression of IL-4, IL-5, IL-9, and IL-13 shows a potential pathogenic role in pulmonary lung disease showing symptoms including breathing difficulty, cough, mucus (sputum), and production and wheezing.

IL-4, IL-5, IL-9, and IL-13 are the secretory products of stimulated macrophages and other cells. The increase in the levels of these cytokines results in inflammation in the respiratory tract including the trachea, bronchi, bronchioles, alveoli, pleural cavity, and muscles of respiration.

As an effective therapy for respiratory lung disease such as Asthma, COPD, etc., provides a ribozyme and ribozyme delivery system which cleaves mRNA encoding cytokines involved in inflammation.

Our intervention is through RNAi which is the process of sequence-specific, transcriptional gene silencing through siRNA. It is a method of controlling gene expression and has potential in the development of drugs for pulmonary lung disease.


A hammerhead ribozyme has two binding arms designed to bind to the complementary RNA targets. The ribozyme binds to its target mRNA and makes an mRNA-ribozyme complex. The catalytic motif of the ribozyme then cleaves its target RNA into fragments and inhibits gene expression. Ribozyme becomes free after cleaving the target RNA and becomes free to enter into the next cycle.

Several molecular factors are involved in the inflammatory process in asthma. Therefore, blocking the function of these factors could efficiently alleviate airway inflammation.

RNA interference (RNAi) is often thought to be the answer while seeking more efficient and biocompatible treatments. However, certain difficulties appear in the efficient delivery of small interference RNA.

The key factor in RNAi, to target cells and tissues, have limited its clinical application. In this review, we have summarized cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors reported as targets of RNA-mediated treatment in experimental asthma. Also, we can conclude that several targeted delivery systems of RNA to specific cells such as T cells, macrophages, and dendritic cells, could potentially be applied in asthma therapy.

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