{"id":187,"date":"2023-02-07T07:44:31","date_gmt":"2023-02-07T07:44:31","guid":{"rendered":"https:\/\/mrna.creative-biolabs.com\/blog\/?p=187"},"modified":"2023-02-07T07:44:31","modified_gmt":"2023-02-07T07:44:31","slug":"an-innovative-inhaled-mrna-therapy-possibly-realizes-precise-delivery-of-mrna-to-lungs","status":"publish","type":"post","link":"https:\/\/mrna.creative-biolabs.com\/blog\/an-innovative-inhaled-mrna-therapy-possibly-realizes-precise-delivery-of-mrna-to-lungs\/","title":{"rendered":"An Innovative Inhaled mRNA Therapy Possibly Realizes Precise Delivery of mRNA to Lungs"},"content":{"rendered":"

Nucleic acid-based drugs are very adaptable and may encode a wide range of therapeutic proteins for treatment, prevention, or vaccine. Currently, the development and improvement of viral vectors such as lentivirus and adeno-associated virus (AAV) as well as non-viral vectors such as lipid nanoparticles (LNP) have substantially aided in the production of nucleic acid drugs.<\/span><\/p>\n

However, current nucleic acid drug delivery systems are prone to drug enrichment in the liver, and a large number of lung diseases, including COVID-19, influenza, cystic fibrosis, and lung cancer, urgently require a vector that can effectively deliver mRNA<\/a><\/strong><\/span> to the lung to advance the prevention and treatment of lung diseases with mRNA vaccines\/therapies.<\/span><\/p>\n

To date, lung-targeted mRNA delivery has been largely academic studies using polyethyleneimine (PEI), lipid nanoparticles (LNPs) in mice, with few clinical trials in humans. One of the best known clinical trials is the nebulized formulation of LNP-delivered mRNA developed by Translate Bio for the treatment of cystic fibrosis, but unfortunately, the lung function of patients did not improve after treatment.<\/span><\/p>\n

Recently, the Philip Santangelo team of Georgia Institute of Technology and Emory University published a paper entitled “Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung” in Nature Materials<\/em>. In this study, a polymer nanoparticle P76 was screened and identified, which can deliver all kinds of mRNA to the lungs of different animals by aerosol inhalation and has great safety and tolerability.<\/span><\/p>\n

Studies in Syrian hamsters showed that P76 can nebulize and inhale mRNA encoding CRISPR-Cas13a to treat SARS-CoV-2 infection, with outstanding induction of neutralizing antibody at a dose of 20.<\/span><\/p>\n

This study proposes a strategy for discovering inhaled polymer formulations that target the lungs, opening new doors to the development of mRNA vaccines<\/a><\/strong><\/span>\/therapies for the prevention or treatment of lung diseases.<\/span><\/p>\n

In this recent study, to improve the delivery of PBAE preparations to the lungs, the team evaluated 166PBAE and PBAE-containing preparations in mice using a combined synthesis strategy and a particle screening system based on a low dead volume nebulizer.<\/span><\/p>\n

In preliminary screening, the team found P76, a poly (\u03b2-aminothioester) (PBATE) that can deliver mRNA to the lungs of mice, hamsters, ferrets, as well as cows and rhesus monkeys, regardless of the length and complexity of mRNA.<\/span><\/p>\n

More importantly, the study found that P76 was safe and well tolerated, and the expression of mRNA given via aerosol inhalation was higher than that of PBAE previously established by the team. Comparative experiments were conducted in Syrian hamsters and the results showed that atomized mRNA delivery of CRISPR-Cas13a by P76 could effectively prevent hamster weight loss caused by SARS-CoV-2 infection, and the dose of P76 (50 mcg) was only a quarter of that of PBAE (200 ug). In addition, the effect of aerosol inhalation administration was comparable to that of direct intraperitoneal injection of high-dose SARS-CoV-2 neutralizing antibody (1000 \u03bcg).<\/span><\/p>\n

Overall, the study identified P76 as an efficient carrier for delivering mRNA through aerosol inhalation, as well as to a variety of animals, including mice, cows, and rhesus monkeys. The study also confirmed that P76 can achieve an efficacy similar to that of the gold standard (systemic neutralization antibody therapy) at a low dose of 1\/20 in Syrian hamsters infected with SARS-CoV-2, with the lowest toxicity. P76 represents a substantial step forward for polymer nanoparticles, making it possible to develop inhaled nucleic acid therapy in the future.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Nucleic acid-based drugs are very adaptable and may encode a wide range of therapeutic proteins for treatment, prevention, or vaccine. Currently, the development and improvement of viral vectors such as lentivirus andRead More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":188,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2,1],"tags":[32,10],"_links":{"self":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/187"}],"collection":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/comments?post=187"}],"version-history":[{"count":2,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/187\/revisions"}],"predecessor-version":[{"id":190,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/187\/revisions\/190"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media\/188"}],"wp:attachment":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media?parent=187"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/categories?post=187"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/tags?post=187"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}