A Multi-Targeted Antisense Oligonucleotide-Based Therapy Directed at Phosphodiesterases 4 and 7 for COPD

Séguin, Rosanne; Ferrari, Nicoletta

doi:10.5772/30294

Cited by 1 publication

(1 citation statement)

References 64 publications

(67 reference statements)

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“…Among the big PDE family, PDE4 is present in many types of cells relating to COPD and thought to be a promising therapeutic target. TPI1100, a dual PDE inhibitor comprising two modified ASOs directing against PDE4B/4D and 7A, was designed to reduce the recruitment and activation of inflammatory cells in COPD and shown to reduce the neutrophil influx in bronchoalveolar lavage (BAL) and inflammation of smoke-exposure or LPS-challenge murine models (84). The phase I clinical trial of TPI1100 was initiated in 2009 but was withdrawn due to drug development suspension.…”

Section: Inflammatory Diseasesmentioning

confidence: 99%

Nucleic Acid-Based Therapeutics for Pulmonary Diseases

et al. 2018

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Nucleic acid-based therapeutics present huge potential in the treatment of pulmonary diseases ranging from lung cancer to asthma and chronic pulmonary diseases, which are often fatal and widely prevalent. The susceptibility of nucleic acids to degradation and the complex structure of lungs retard the effective pulmonary delivery of nucleic acid drug. To overcome these barriers, different strategies have been exploited to increase the delivery efficiency using chemically synthesized nucleic acids, vector encapsulation, proper formulation, and administration route. However, several limitations regarding off-target effects and immune stimulation of nucleic acid drugs hamper their translation into the clinical practice. Therefore, their successful clinical application will ultimately rely on well-developed carriers and methods to ensure safety and efficacy. In this review, we provide a comprehensive overview of the nucleic acid application for pulmonary diseases, covering action mechanism of the nucleic acid drugs, the novel delivery systems, and the current formulation for the administration to lungs. The latest advances of nucleic acid drugs under clinical evaluation to treat pulmonary disorders will also be detailed.KEY WORDS: nucleic acid; antisense oligonucleotide (ASO); short interfering RNA (siRNA); microRNA (miRNA); pulmonary diseases.

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Section: Inflammatory Diseasesmentioning

confidence: 99%