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Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis
- Publication Year :
- 2016
-
Abstract
- Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment.
- Subjects :
- 0301 basic medicine
Small interfering RNA
Tuberculosis
Antitubercular Agents
Pharmaceutical Science
Drug resistance
RNAi delivery
Host-directed therapy
RNAi Therapeutics
Mycobacterium tuberculosis
03 medical and health sciences
0302 clinical medicine
RNA interference
Administration, Inhalation
Tuberculosis, Multidrug-Resistant
Humans
Medicine
Gene silencing
Pulmonary delivery
Tuberculosis, Pulmonary
biology
business.industry
MicroRNA
medicine.disease
biology.organism_classification
Multiple drug resistance
030104 developmental biology
Inhalation
030220 oncology & carcinogenesis
Immunology
Non-viral vectors
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b816d7c2e51f0a59fbcf6862cc6216ea