Can pulmonary RNA delivery improve our pandemic preparedness?

Merkel, Olivia M.

doi:10.1016/j.jconrel.2022.03.039

Cited by 10 publications

(2 citation statements)

References 85 publications

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“…Although the use of spray drying for inhalable gene therapy assures manageable tools to obtain NEMs with appropriate aerodynamic properties for lung deposition, the technique also needs to ensure the stability of the nucleic acid-based cargo [ 139 ]. Therefore, studying and adjusting spray drying parameters is crucial for nucleic acid-loaded NEM development.…”

Section: Pulmonary Administrationmentioning

confidence: 99%

Shaping the future from the small scale: dry powder inhalation of CRISPR-Cas9 lipid nanoparticles for the treatment of lung diseases

Carneiro

Greco

Chiesa

et al. 2023

Expert Opinion on Drug Delivery

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Introduction Most lung diseases are serious conditions resulting from genetic and environmental causes associated with high mortality and severe symptoms. Currently, treatments available have a palliative effect and many targets are still considered undruggable. Gene therapy stands as an attractive approach to offering innovative therapeutic solutions. CRISPR-Cas9 has established a remarkable potential for genome editing with high selectivity to targeted mutations. To ensure high efficacy with minimum systemic exposure, the delivery and administration route are key components that must be investigated. Areas covered This review is focused on the delivery of CRISPR-Cas9 to the lungs, taking advantage of lipid nanoparticles (LNPs), the most clinically advanced nucleic acid carriers. We also aim to highlight the benefits of pulmonary administration as a local delivery route and the use of spray drying to prepare stable nucleic acid-based dry powder formulations able to overcome multiple lung barriers. Expert opinion Exploring the pulmonary administration to deliver CRISPR-Cas9 loaded in LNPs as a dry powder increases the chances to achieve high efficacy and reduced adverse effects. CRISPR-Cas9 loaded in LNP-embedded microparticles has not yet been reported in the literature but has the potential to reach and accumulate in target cells in the lung, thus, enhancing overall efficacy and safety.

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Section: Pulmonary Administrationmentioning

confidence: 99%

Shaping the future from the small scale: dry powder inhalation of CRISPR-Cas9 lipid nanoparticles for the treatment of lung diseases

Carneiro

Greco

Chiesa

et al. 2023

Expert Opinion on Drug Delivery

Self Cite

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“…The emergence of Omicron variant indicates how fast the SARS-CoV-2 evolves, and its potential impact on the current protein-based intervention (i.e., vaccines, antibodies, or convalescent plasma) that primarily targets the highly mutated Spike (S) protein cannot be neglected [7]. One emerging concept in anti-COVID-19 medication involves the development of nucleic acid-based therapeutics, which can degrade the viral genome and can be quickly adjusted to viral mutations [8][9][10]. Nucleic acid-based therapeutics include small interfering RNAs (siRNAs).…”

Section: Introductionmentioning

confidence: 99%

RNAi Degrades Spike Protein Gene Transcripts of the SARS-CoV-2 for Developing Drugs to Treat of COVID-19

Zhang¹,

Huang²,

Huang³

et al. 2022

Nano BioMed ENG

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COVID-19 is caused by severe acute respiratory SARS-CoV-2. Regardless of the availability of treatment strategies for COVID-19, effective therapy will remain essential. A promising approach to tackle the SARS-CoV-2 could be small interfering (si) RNAs. Here we designed the small hairpin RNA (named as shRNA688) for targeting the prepared 813 bp Est of the S protein genes (Delta). The conserved and mutated regions of the S protein genes from the genomes of the SARS-CoV-2 variants in the public database were analyzed. A 813 bp fragment encoding the most part of the RBD and partial downstream RBD of the S protein was cloned into the upstream red florescent protein gene (RFP) as a fusing gene in the pCMV-S-Protein RBD-Est-RFP plasmid for expressing a potential target for RNAi. The double stranded of the DNA encoding for shRNA688 was constructed in the downstream human H1 promoter of the plasmid in which CMV promoter drives enhanced green fluorescent protein (EGFP) marker gene expression. These two kinds of the constructed plasmids were co-transfected into HEK293T via Lipofectamine 2000. The degradation of the transcripts of the SARS-CoV-2 S protein fusing gene expressed in the transfected HEK293T treated by RNAi was analyzed by RT-qPCR with a specific probe of the targeted SARS-CoV-2 S protein gene transcripts. Our results showed that shRNA688 targeting the conserved region of the S protein genes could effectively reduce the transcripts of the S protein genes. This study provides a cell model and technical support for the research and development of the broad-spectrum small nucleic acid RNAi drugs against SARS-CoV-2 or the RNAi drugs for the other hazard viruses which cause human diseases.

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Engineering of Hydrogels for Pulmonary Drug Delivery: Opportunities and Challenges

Dhapte‐Pawar

Polshettiwar

Mehta

2023

Pulmonary Drug Delivery Systems: Material and Technological Advances

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Can pulmonary RNA delivery improve our pandemic preparedness?

Cited by 10 publications

References 85 publications

Shaping the future from the small scale: dry powder inhalation of CRISPR-Cas9 lipid nanoparticles for the treatment of lung diseases

Shaping the future from the small scale: dry powder inhalation of CRISPR-Cas9 lipid nanoparticles for the treatment of lung diseases

RNAi Degrades Spike Protein Gene Transcripts of the SARS-CoV-2 for Developing Drugs to Treat of COVID-19

Engineering of Hydrogels for Pulmonary Drug Delivery: Opportunities and Challenges

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