Zephyrnet Logo

Combinatorial development of nebulized mRNA delivery formulations for the lungs – Nature Nanotechnology

Date:

  • Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol. Ther. 27, 710–728 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Hajj, K. A. & Whitehead, K. A. Tools for translation: non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2, 1–17 (2017).

    Article 

    Google Scholar
     

  • Han, X. et al. An ionizable lipid toolbox for RNA delivery. Nat. Commun. 12, 7233 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Qiu, M. et al. Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3. Proc. Natl Acad. Sci. USA 118, e2020401118 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Swingle, K. L., Hamilton, A. G. & Mitchell, M. J. Lipid nanoparticle-mediated delivery of mRNA therapeutics and vaccines. Trends Mol. Med. 27, 616–617 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Miao, L. et al. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Zhang, X. et al. Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing. Sci. Adv. 6, eabc2315 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Billingsley, M. M. et al. Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett. 20, 1578–1589 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Riley, R. S. et al. Ionizable lipid nanoparticles for in utero mRNA delivery. Sci. Adv. 7, eaba1028 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Sabnis, S. et al. A novel amino lipid series for mRNA delivery: improved endosomal escape and sustained pharmacology and safety in non-human primates. Mol. Ther. 26, 1509–1519 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Fenton, O. S. et al. Synthesis and biological evaluation of ionizable lipid materials for the in vivo delivery of messenger RNA to B lymphocytes. Adv. Mater. 29, 1606944 (2017).

    Article 

    Google Scholar
     

  • Liu, J. et al. Fast and efficient CRISPR/Cas9 genome editing in vivo enabled by bioreducible lipid and messenger RNA nanoparticles. Adv. Mater. 31, 1902575 (2019).

    Article 

    Google Scholar
     

  • Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Gillmore, J. D. et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Cornebise, M. et al. Discovery of a novel amino lipid that improves lipid nanoparticle performance through specific interactions with mRNA. Adv. Funct. Mater. https://doi.org/10.1002/adfm.202106727 (2021).

  • Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R. & Anderson, D. G. The clinical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 40, 840–854 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Chakraborty, C., Sharma, A. R., Bhattacharya, M. & Lee, S.-S. From COVID-19 to cancer mRNA vaccines: moving from bench to clinic in the vaccine landscape. Front. Immunol. 12, 2648 (2021).

    Article 

    Google Scholar
     

  • Cafri, G. et al. mRNA vaccine-induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer. J. Clin. Invest. 130, 5976–5988 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Oberli, M. A. et al. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 17, 1326–1335 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Espeseth, A. S. et al. Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic and protective in rodent models of RSV infection. NPJ Vaccines 5, 1–14 (2020).

    Article 

    Google Scholar
     

  • Aliprantis, A. O. et al. A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults. Hum. Vaccines Immunother. 17, 1248–1261 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol. Ther. 25, 1316–1327 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Feldman, R. A. et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019).

    Article 
    CAS 

    Google Scholar
     

  • John, S. et al. Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. Vaccine 36, 1689–1699 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Medina-Magües, L. G. et al. mRNA vaccine protects against zika virus. Vaccines 9, 1464 (2021).

    Article 

    Google Scholar
     

  • Mu, Z., Haynes, B. F. & Cain, D. W. HIV mRNA vaccines—progress and future paths. Vaccines 9, 134 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Zabaleta, N., Torella, L., Weber, N. D. & Gonzalez-Aseguinolaza, G. mRNA and gene editing: late breaking therapies in liver diseases. Hepatology https://doi.org/10.1002/hep.32441 (2022).

  • Robinson, E. et al. Lipid nanoparticle-delivered chemically modified mRNA restores chloride secretion in cystic fibrosis. Mol. Ther. 26, 2034–2046 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Da Silva Sanchez, A., Paunovska, K., Cristian, A. & Dahlman, J. E. Treating cystic fibrosis with mRNA and CRISPR. Hum. Gene Ther. 31, 940–955 (2020).

    Article 

    Google Scholar
     

  • Lai, M. et al. Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia. J. Med. Genet. 53, 242–249 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Paff, T., Omran, H., Nielsen, K. G. & Haarman, E. G. Current and future treatments in primary ciliary dyskinesia. Int. J. Mol. Sci. 22, 9834 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Guan, S., Darmstädter, M., Xu, C. & Rosenecker, J. In vitro investigations on optimizing and nebulization of IVT-mRNA formulations for potential pulmonary-based α-1-antitrypsin deficiency treatment. Pharmaceutics 13, 1281 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Zeyer, F. et al. mRNA-mediated gene supplementation of Toll-like receptors as treatment strategy for asthma in vivo. PLoS ONE 11, e0154001 (2016).

    Article 

    Google Scholar
     

  • Mays, L. E. et al. Modified Foxp3 mRNA protects against asthma through an IL-10–dependent mechanism. J. Clin. Invest. 123, 1216–1228 (2013).

    Article 
    CAS 

    Google Scholar
     

  • Rakhra, K. et al. Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells. Sci. Immunol. 6, eabd8003 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Bivas-Benita, M. et al. Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis. Vaccine 22, 1609–1615 (2004).

    Article 
    CAS 

    Google Scholar
     

  • Rajapaksa, A. E. et al. Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization. Respir. Res. 15, 60 (2014).

    Article 

    Google Scholar
     

  • Wu, M. et al. Intranasal vaccination with mannosylated chitosan formulated DNA vaccine enables robust IgA and cellular response induction in the lungs of mice and improves protection against pulmonary mycobacterial challenge. Front. Cell. Infect. Microbiol. 7, 445 (2017).

    Article 

    Google Scholar
     

  • King, R. G. et al. Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 and fully protects mice from lethal challenge. Vaccines 9, 881 (2021).

    Article 
    CAS 

    Google Scholar
     

  • An, X. et al. Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2. iScience 24, 103037 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Kim, Y. C. et al. Strategy to enhance dendritic cell-mediated DNA vaccination in the lung. Adv. Ther. 3, 2000013 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Lu, D. & Hickey, A. J. Pulmonary vaccine delivery. Expert Rev. Vaccines 6, 213–226 (2007).

    Article 
    CAS 

    Google Scholar
     

  • Sou, T. et al. New developments in dry powder pulmonary vaccine delivery. Trends Biotechnol. 29, 191–198 (2011).

    Article 
    CAS 

    Google Scholar
     

  • Huang, J. et al. A novel dry powder influenza vaccine and intranasal delivery technology: induction of systemic and mucosal immune responses in rats. Vaccine 23, 794–801 (2004).

    Article 
    CAS 

    Google Scholar
     

  • Minne, A. et al. The delivery site of a monovalent influenza vaccine within the respiratory tract impacts on the immune response. Immunology 122, 316–325 (2007).

    Article 
    CAS 

    Google Scholar
     

  • Wang, Z. et al. Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine. Nat. Biomed. Eng. 6, 791–805 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Patel, A. K. et al. Inhaled nanoformulated mRNA polyplexes for protein production in lung epithelium. Adv. Mater. 31, 1805116 (2019).

    Article 

    Google Scholar
     

  • Lokugamage, M. P. et al. Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs. Nat. Biomed. Eng. 5, 1059–1068 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Wilson, C. Future therapies for cystic fibrosis. Lancet Respir. Med. 10, e75–e76 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Witten, J., Samad, T. & Ribbeck, K. Selective permeability of mucus barriers. Curr. Opin. Biotechnol. 52, 124–133 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Witten, J. & Ribbeck, K. The particle in the spider’s web: transport through biological hydrogels. Nanoscale 9, 8080–8095 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Cone, R. A. Barrier properties of mucus. Adv. Drug Deliv. Rev. 61, 75–85 (2009).

    Article 
    CAS 

    Google Scholar
     

  • Lieleg, O. & Ribbeck, K. Biological hydrogels as selective diffusion barriers. Trends Cell Biol. 21, 543–551 (2011).

    Article 
    CAS 

    Google Scholar
     

  • Kim, N., Duncan, G. A., Hanes, J. & Suk, J. S. Barriers to inhaled gene therapy of obstructive lung diseases: a review. J. Controlled Release 240, 465–488 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Coyne, C. B., Kelly, M. M., Boucher, R. C. & Johnson, L. G. Enhanced epithelial gene transfer by modulation of tight junctions with sodium caprate. Am. J. Respir. Cell Mol. Biol. 23, 602–609 (2000).

    Article 
    CAS 

    Google Scholar
     

  • Kauffman, K. J. et al. Optimization of lipid nanoparticle formulations for mRNA delivery in vivo with fractional factorial and definitive screening designs. Nano Lett. 15, 7300–7306 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Billingsley, M. M. et al. Orthogonal design of experiments for optimization of lipid nanoparticles for mRNA engineering of CAR T cells. Nano Lett. 22, 533–542 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Li, S. et al. Payload distribution and capacity of mRNA lipid nanoparticles. Nat. Commun. 13, 5561 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Kauffman, K. J. et al. Rapid, single-cell analysis and discovery of vectored mRNA transfection in vivo with a loxP-flanked tdTomato reporter mouse. Mol. Ther. Nucleic Acids 10, 55–63 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Ball, R. L., Bajaj, P. & Whitehead, K. A. Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization. Int. J. Nanomed. 12, 305–315 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Zhao, P. et al. Long-term storage of lipid-like nanoparticles for mRNA delivery. Bioact. Mater. 5, 358–363 (2020).


    Google Scholar
     

  • Crowe, J. H., Oliver, A. E., Hoekstra, F. A. & Crowe, L. M. Stabilization of dry membranes by mixtures of hydroxyethyl starch and glucose: the role of vitrification. Cryobiology 35, 20–30 (1997).

    Article 
    CAS 

    Google Scholar
     

  • Ohtake, S., Schebor, C., Palecek, S. P. & de Pablo, J. J. Phase behavior of freeze-dried phospholipid–cholesterol mixtures stabilized with trehalose. Biochim. Biophys. Acta Biomembr. 1713, 57–64 (2005).

    Article 
    CAS 

    Google Scholar
     

  • Eastman, S. J. et al. Optimization of formulations and conditions for the aerosol delivery of functional cationic lipid:DNA complexes. Hum. Gene Ther. 8, 313–322 (1997).

    Article 
    CAS 

    Google Scholar
     

  • Whitehead, K. A. et al. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat. Commun. 5, 4277 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR–Cas gene editing. Nat. Mater. 20, 701–710 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Pezzulo, A. A. et al. The air–liquid interface and use of primary cell cultures are important to recapitulate the transcriptional profile of in vivo airway epithelia. Am. J. Physiol. Lung Cell. Mol. Physiol. 300, L25–L31 (2011).

    Article 
    CAS 

    Google Scholar
     

  • Hill, D. B. & Button, B. in Mucins: Methods and Protocols (eds McGuckin, M. A. & Thornton, D. J.) 245–258 (Humana Press, 2012); https://doi.org/10.1007/978-1-61779-513-8_15

  • Ramachandran, S. et al. Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro. Am. J. Physiol. Lung Cell. Mol. Physiol. 305, L23–L32 (2013).

    Article 
    CAS 

    Google Scholar
     

  • Krishnamurthy, S. et al. Manipulation of cell physiology enables gene silencing in well-differentiated airway epithelia. Mol. Ther. Nucleic Acids 1, e41 (2012).

    Article 

    Google Scholar
     

  • Burgel, P.-R., Montani, D., Danel, C., Dusser, D. J. & Nadel, J. A. A morphometric study of mucins and small airway plugging in cystic fibrosis. Thorax 62, 153–161 (2007).

    Article 

    Google Scholar
     

  • Ratjen, F. Cystic fibrosis: the role of the small airways. J. Aerosol Med. Pulm. Drug Deliv. 25, 261–264 (2012).

    Article 

    Google Scholar
     

  • van den Berge, M., ten Hacken, N. H. T., Cohen, J., Douma, W. R. & Postma, D. S. Small airway disease in asthma and COPD: clinical implications. Chest 139, 412–423 (2011).

    Article 

    Google Scholar
     

  • Tiddens, H. A. W. M., Donaldson, S. H., Rosenfeld, M. & Paré, P. D. Cystic fibrosis lung disease starts in the small airways: can we treat it more effectively? Pediatr. Pulmonol. 45, 107–117 (2010).

    Article 

    Google Scholar
     

  • Tatsuta, M. et al. Effects of cigarette smoke on barrier function and tight junction proteins in the bronchial epithelium: protective role of cathelicidin LL-37. Respir. Res. 20, 251 (2019).

    Article 

    Google Scholar
     

  • Maeki, M., Uno, S., Niwa, A., Okada, Y. & Tokeshi, M. Microfluidic technologies and devices for lipid nanoparticle-based RNA delivery. J. Control. Release 344, 80–96 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Cheng, M. H. Y. et al. Induction of bleb structures in lipid nanoparticle formulations of mRNA leads to improved transfection potency. Adv. Mater. https://doi.org/10.1002/adma.202303370 (2023).

  • Brader, M. L. et al. Encapsulation state of messenger RNA inside lipid nanoparticles. Biophys. J. 120, 2766–2770 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Kulkarni, J. A. et al. On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA. ACS Nano 12, 4787–4795 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Kulkarni, J. A. et al. Fusion-dependent formation of lipid nanoparticles containing macromolecular payloads. Nanoscale 11, 9023–9031 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Richardson, S. J., Bai, A., Kulkarni, A. A. & Moghaddam, M. F. Efficiency in drug discovery: liver S9 fraction assay as a screen for metabolic stability. Drug Metab. Lett. 10, 83–90 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Scholte, B. J., Davidson, D. J., Wilke, M. & de Jonge, H. R. Animal models of cystic fibrosis. J. Cyst. Fibros. 3, 183–190 (2004).

    Article 
    CAS 

    Google Scholar
     

  • McCarron, A., Donnelley, M. & Parsons, D. Airway disease phenotypes in animal models of cystic fibrosis. Respir. Res. 19, 54 (2018).

    Article 

    Google Scholar
     

  • Kim, N. et al. Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier. Thorax 77, 812–820 (2022).

    Article 

    Google Scholar
     

  • Phillips, J. E., Zhang, X. & Johnston, J. A. Dry powder and nebulized aerosol inhalation of pharmaceuticals delivered to mice using a nose-only exposure system. J. Vis. Exp. https://doi.org/10.3791/55454 (2017).

  • Beck, S. E. et al. Deposition and expression of aerosolized rAAV vectors in the lungs of rhesus macaques. Mol. Ther. 6, 546–554 (2002).

    Article 
    CAS 

    Google Scholar
     

  • Woo, C. J. et al. Inhaled delivery of a lipid nanoparticle encapsulated messenger RNA encoding a ciliary protein for the treatment of primary ciliary dyskinesia. Pulm. Pharmacol. Ther. 75, 102134 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Okuda, K. et al. Secretory cells dominate airway CFTR expression and function in human airway superficial epithelia. Am. J. Respir. Crit. Care Med. 203, 1275–1289 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Carraro, G. et al. Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition. Nat. Med. 27, 806–814 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Hodges, C. A. & Conlon, R. A. Delivering on the promise of gene editing for cystic fibrosis. Genes Dis. 6, 97–108 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Vanover, D. et al. Nebulized mRNA-encoded antibodies protect hamsters from SARS-CoV-2 infection. Adv. Sci. 9, 2202771 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Rhym, L. H., Manan, R. S., Koller, A., Stephanie, G. & Anderson, D. G. Peptide-encoding mRNA barcodes for the high-throughput in vivo screening of libraries of lipid nanoparticles for mRNA delivery. Nat. Biomed. Eng. 7, 901–910 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Chen, D. et al. Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J. Am. Chem. Soc. 134, 6948–6951 (2012).

    Article 
    CAS 

    Google Scholar
     

  • Heyes, J., Palmer, L., Bremner, K. & MacLachlan, I. Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids. J. Control. Release 107, 276–287 (2005).

    Article 
    CAS 

    Google Scholar
     

  • spot_img

    Latest Intelligence

    spot_img