Nucleic Acid-Based Therapeutics for Pulmonary
Diseases

Chen, Jing; Tang, Yue; Liu, Yun; Dou, Yushun

doi:10.1208/s12249-018-1183-0

Cited by 34 publications

(10 citation statements)

References 96 publications

(93 reference statements)

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“…Gene replacement can also be achieved by encapsulating plasmid DNA. This approach is being evaluated for treating lung cancer [217] and inflammatory diseases [218]. Inhaled gene-expressing plasmids therapy gives hope to chronic airway inflammatory disease such as allergic asthma, where a combination of mucus penetrating nanoparticle demonstrated anti-inflammatory and anti-fibrotic effects [219,220].…”

Section: Lipid-based Pulmonary Gene Therapy and Vaccinationmentioning

confidence: 99%

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Artzy‐Schnirman

Raviv

Flikshtain

et al. 2021

Advanced Drug Delivery Reviews

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Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant in vitro pulmonary platforms. Notably, in vitro strategies using foremost lung-on-chips and biocompatible "soft" membranes have focused on platforms that emphasize phenotypical endpoints recapitulating key physiological and cellular functions. We review some of the most recent in vitro studies underlining seminal therapeutic screens and translational applications and open our discussion to promising avenues of pulmonary therapeutic exploration focusing on liposomes. Undeniably, there still remains a recognized trade-off between the physiological and biological complexity of these novel in vitro lung models and their ability to deliver assays with throughput capabilities. The upcoming years are thus anticipated to see further developments in broadening the applicability of such in vitro systems and accelerating therapeutic exploration for drug discovery and translational medicine in treating respiratory disorders.

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Section: Lipid-based Pulmonary Gene Therapy and Vaccinationmentioning

confidence: 99%

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Artzy‐Schnirman

Raviv

Flikshtain

et al. 2021

Advanced Drug Delivery Reviews

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“…Data have shown long-term treatment and frequent administration were often increase the immunogenicity of biological drug products 195 , which should be critically evaluated during the development of the inhaled formulations with extended pulmonary exposure using sustained-release formulations. Besides protein and peptide drugs, the immunogenicity of the nucleic acid-based therapeutics such as DNA, RNA species or analogues and their vectors often hinder their translations into the clinical practice 196 . The extracellular DNA can be recognized by immune cell receptors as damage-related molecular patterns or pathogen-related molecular patterns, activating pro-inflammatory signaling pathways or immunosuppressive cell functions 197 .…”

Section: Safety Concerns In Designing Of Inhaled Formulations With Extended Pulmonary Exposurementioning

confidence: 99%

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

Guo

Bera

Shi

et al. 2021

Acta Pharmaceutica Sinica B

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Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma, chronic obstructive pulmonary diseases and respiratory infections, and systemic diseases such as diabetes. Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit. The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration, but also enhance the clinical benefits to the patients with improved therapeutic outcomes. This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines. It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure, which is followed by recent advances in various strategies to overcome these barriers. Finally, the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

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“…And both approaches are accompanied by hurdles and challenges. [ 106 ] While in vivo studies in rodents can be performed using intratracheal aerosolization with one of three different devices, the PennCentury Microsprayer, [ 99 ] the Micro‐Mist Nebulizer, [ 107 ] and the AeroProbe nebulizing catheter, [ 108 ] development of a product would require formulation development accordingly.…”

Section: The Sars‐cov‐2 Pandemic—a Case Study For Rnai Therapeuticsmentioning

confidence: 99%

siRNA Therapeutics against Respiratory Viral Infections—What Have We Learned for Potential COVID‐19 Therapies?

Mehta

Michler

Merkel

2021

Adv Healthcare Materials

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Acute viral respiratory tract infections (AVRIs) are a major burden on human health and global economy and amongst the top five causes of death worldwide resulting in an estimated 3.9 million lives lost every year. In addition, new emerging respiratory viruses regularly cause outbreaks such as SARS‐CoV‐1 in 2003, the "Swine flu" in 2009, or most importantly the ongoing SARS‐CoV‐2 pandemic, which intensely impact global health, social life, and economy. Despite the prevalence of AVRIs and an urgent need, no vaccines—except for influenza—or effective treatments were available at the beginning of the COVID‐19 pandemic. However, the innate RNAi pathway offers the ability to develop nucleic acid‐based antiviral drugs. siRNA sequences against conserved, essential regions of the viral genome can prevent viral replication. In addition, viral infection can be averted prophylactically by silencing host genes essential for host–viral interactions. Unfortunately, delivering siRNAs to their target cells and intracellular site of action remains the principle hurdle toward their therapeutic use. Currently, siRNA formulations and chemical modifications are evaluated for their delivery. This progress report discusses the selection of antiviral siRNA sequences, delivery techniques to the infection sites, and provides an overview of antiviral siRNAs against respiratory viruses.

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Nucleic Acid-Based Therapeutics for Pulmonary Diseases

Cited by 34 publications

References 96 publications

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

siRNA Therapeutics against Respiratory Viral Infections—What Have We Learned for Potential COVID‐19 Therapies?

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