Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in applied sciences for therapeutic mRNA supply. Mol. Ther. 27, 710–728 (2019).
Hajj, Okay. A. & Whitehead, Okay. A. Instruments for translation: non-viral supplies for therapeutic mRNA supply. Nat. Rev. Mater. 2, 1–17 (2017).
Han, X. et al. An ionizable lipid toolbox for RNA supply. Nat. Commun. 12, 7233 (2021).
Qiu, M. et al. Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome enhancing of Angptl3. Proc. Natl Acad. Sci. USA 118, e2020401118 (2021).
Swingle, Okay. L., Hamilton, A. G. & Mitchell, M. J. Lipid nanoparticle-mediated supply of mRNA therapeutics and vaccines. Traits Mol. Med. 27, 616–617 (2021).
Miao, L. et al. Supply of mRNA vaccines with heterocyclic lipids will increase anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019).
Zhang, X. et al. Functionalized lipid-like nanoparticles for in vivo mRNA supply and base enhancing. Sci. Adv. 6, eabc2315 (2020).
Billingsley, M. M. et al. Ionizable lipid nanoparticle-mediated mRNA supply for human CAR T cell engineering. Nano Lett. 20, 1578–1589 (2020).
Riley, R. S. et al. Ionizable lipid nanoparticles for in utero mRNA supply. Sci. Adv. 7, eaba1028 (2021).
Sabnis, S. et al. A novel amino lipid sequence for mRNA supply: improved endosomal escape and sustained pharmacology and security in non-human primates. Mol. Ther. 26, 1509–1519 (2018).
Fenton, O. S. et al. Synthesis and organic analysis of ionizable lipid supplies for the in vivo supply of messenger RNA to B lymphocytes. Adv. Mater. 29, 1606944 (2017).
Liu, J. et al. Quick and environment friendly CRISPR/Cas9 genome enhancing in vivo enabled by bioreducible lipid and messenger RNA nanoparticles. Adv. Mater. 31, 1902575 (2019).
Polack, F. P. et al. Security and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).
Baden, L. R. et al. Efficacy and security of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021).
Gillmore, J. D. et al. CRISPR-Cas9 in vivo gene enhancing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).
Cornebise, M. et al. Discovery of a novel amino lipid that improves lipid nanoparticle efficiency via particular 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 scientific progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 40, 840–854 (2022).
Chakraborty, C., Sharma, A. R., Bhattacharya, M. & Lee, S.-S. From COVID-19 to most cancers mRNA vaccines: shifting from bench to clinic within the vaccine panorama. Entrance. Immunol. 12, 2648 (2021).
Cafri, G. et al. mRNA vaccine-induced neoantigen-specific T cell immunity in sufferers with gastrointestinal most cancers. J. Clin. Make investments. 130, 5976–5988 (2020).
Oberli, M. A. et al. Lipid nanoparticle assisted mRNA supply for potent most cancers immunotherapy. Nano Lett. 17, 1326–1335 (2017).
Espeseth, A. S. et al. Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic and protecting in rodent fashions of RSV an infection. NPJ Vaccines 5, 1–14 (2020).
Aliprantis, A. O. et al. A section 1, randomized, placebo-controlled research to judge the protection and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in wholesome youthful and older adults. Hum. Vaccines Immunother. 17, 1248–1261 (2021).
Bahl, Okay. et al. Preclinical and scientific demonstration of immunogenicity by mRNA vaccines in opposition to H10N8 and H7N9 influenza viruses. Mol. Ther. 25, 1316–1327 (2017).
Feldman, R. A. et al. mRNA vaccines in opposition to H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and properly tolerated in wholesome adults in section 1 randomized scientific trials. Vaccine 37, 3326–3334 (2019).
John, S. et al. Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. Vaccine 36, 1689–1699 (2018).
Medina-Magües, L. G. et al. mRNA vaccine protects in opposition to zika virus. Vaccines 9, 1464 (2021).
Mu, Z., Haynes, B. F. & Cain, D. W. HIV mRNA vaccines—progress and future paths. Vaccines 9, 134 (2021).
Zabaleta, N., Torella, L., Weber, N. D. & Gonzalez-Aseguinolaza, G. mRNA and gene enhancing: late breaking therapies in liver ailments. 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).
Da Silva Sanchez, A., Paunovska, Okay., Cristian, A. & Dahlman, J. E. Treating cystic fibrosis with mRNA and CRISPR. Hum. Gene Ther. 31, 940–955 (2020).
Lai, M. et al. Gene enhancing of DNAH11 restores regular cilia motility in major ciliary dyskinesia. J. Med. Genet. 53, 242–249 (2016).
Paff, T., Omran, H., Nielsen, Okay. G. & Haarman, E. G. Present and future therapies in major ciliary dyskinesia. Int. J. Mol. Sci. 22, 9834 (2021).
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 remedy. Pharmaceutics 13, 1281 (2021).
Zeyer, F. et al. mRNA-mediated gene supplementation of Toll-like receptors as remedy technique for bronchial asthma in vivo. PLoS ONE 11, e0154001 (2016).
Mays, L. E. et al. Modified Foxp3 mRNA protects in opposition to bronchial asthma via an IL-10–dependent mechanism. J. Clin. Make investments. 123, 1216–1228 (2013).
Rakhra, Okay. et al. Exploiting albumin as a mucosal vaccine chaperone for strong era of lung-resident reminiscence T cells. Sci. Immunol. 6, eabd8003 (2021).
Bivas-Benita, M. et al. Pulmonary supply 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).
Rajapaksa, A. E. et al. Efficient pulmonary supply of an aerosolized plasmid DNA vaccine through floor acoustic wave nebulization. Respir. Res. 15, 60 (2014).
Wu, M. et al. Intranasal vaccination with mannosylated chitosan formulated DNA vaccine allows strong IgA and mobile response induction within the lungs of mice and improves safety in opposition to pulmonary mycobacterial problem. Entrance. Cell. Infect. Microbiol. 7, 445 (2017).
King, R. G. et al. Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity in opposition to SARS-CoV-2 and totally protects mice from deadly problem. Vaccines 9, 881 (2021).
An, X. et al. Single-dose intranasal vaccination elicits systemic and mucosal immunity in opposition to SARS-CoV-2. iScience 24, 103037 (2021).
Kim, Y. C. et al. Technique to reinforce dendritic cell-mediated DNA vaccination within the lung. Adv. Ther. 3, 2000013 (2020).
Lu, D. & Hickey, A. J. Pulmonary vaccine supply. Professional Rev. Vaccines 6, 213–226 (2007).
Sou, T. et al. New developments in dry powder pulmonary vaccine supply. Traits Biotechnol. 29, 191–198 (2011).
Huang, J. et al. A novel dry powder influenza vaccine and intranasal supply expertise: induction of systemic and mucosal immune responses in rats. Vaccine 23, 794–801 (2004).
Minne, A. et al. The supply website of a monovalent influenza vaccine inside the respiratory tract impacts on the immune response. Immunology 122, 316–325 (2007).
Wang, Z. et al. Exosomes adorned with a recombinant SARS-CoV-2 receptor-binding area as an inhalable COVID-19 vaccine. Nat. Biomed. Eng. 6, 791–805 (2022).
Patel, A. Okay. et al. Inhaled nanoformulated mRNA polyplexes for protein manufacturing in lung epithelium. Adv. Mater. 31, 1805116 (2019).
Lokugamage, M. P. et al. Optimization of lipid nanoparticles for the supply of nebulized therapeutic mRNA to the lungs. Nat. Biomed. Eng. 5, 1059–1068 (2021).
Wilson, C. Future therapies for cystic fibrosis. Lancet Respir. Med. 10, e75–e76 (2022).
Witten, J., Samad, T. & Ribbeck, Okay. Selective permeability of mucus boundaries. Curr. Opin. Biotechnol. 52, 124–133 (2018).
Witten, J. & Ribbeck, Okay. The particle within the spider’s internet: transport via organic hydrogels. Nanoscale 9, 8080–8095 (2017).
Cone, R. A. Barrier properties of mucus. Adv. Drug Deliv. Rev. 61, 75–85 (2009).
Lieleg, O. & Ribbeck, Okay. Organic hydrogels as selective diffusion boundaries. Traits Cell Biol. 21, 543–551 (2011).
Kim, N., Duncan, G. A., Hanes, J. & Suk, J. S. Boundaries to inhaled gene remedy of obstructive lung ailments: a evaluation. J. Managed Launch 240, 465–488 (2016).
Coyne, C. B., Kelly, M. M., Boucher, R. C. & Johnson, L. G. Enhanced epithelial gene switch by modulation of tight junctions with sodium caprate. Am. J. Respir. Cell Mol. Biol. 23, 602–609 (2000).
Kauffman, Okay. J. et al. Optimization of lipid nanoparticle formulations for mRNA supply in vivo with fractional factorial and definitive screening designs. Nano Lett. 15, 7300–7306 (2015).
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).
Li, S. et al. Payload distribution and capability of mRNA lipid nanoparticles. Nat. Commun. 13, 5561 (2022).
Kauffman, Okay. J. et al. Fast, single-cell evaluation and discovery of vectored mRNA transfection in vivo with a loxP-flanked tdTomato reporter mouse. Mol. Ther. Nucleic Acids 10, 55–63 (2018).
Ball, R. L., Bajaj, P. & Whitehead, Okay. A. Reaching long-term stability of lipid nanoparticles: inspecting the impact of pH, temperature, and lyophilization. Int. J. Nanomed. 12, 305–315 (2017).
Zhao, P. et al. Lengthy-term storage of lipid-like nanoparticles for mRNA supply. Bioact. Mater. 5, 358–363 (2020).
Crowe, J. H., Oliver, A. E., Hoekstra, F. A. & Crowe, L. M. Stabilization of dry membranes by mixtures of hydroxyethyl starch and glucose: the function of vitrification. Cryobiology 35, 20–30 (1997).
Ohtake, S., Schebor, C., Palecek, S. P. & de Pablo, J. J. Section habits of freeze-dried phospholipid–ldl cholesterol mixtures stabilized with trehalose. Biochim. Biophys. Acta Biomembr. 1713, 57–64 (2005).
Eastman, S. J. et al. Optimization of formulations and situations for the aerosol supply of useful cationic lipid:DNA complexes. Hum. Gene Ther. 8, 313–322 (1997).
Whitehead, Okay. A. et al. Degradable lipid nanoparticles with predictable in vivo siRNA supply exercise. Nat. Commun. 5, 4277 (2014).
Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA supply and CRISPR–Cas gene enhancing. Nat. Mater. 20, 701–710 (2021).
Pezzulo, A. A. et al. The air–liquid interface and use of major cell cultures are essential to recapitulate the transcriptional profile of in vivo airway epithelia. Am. J. Physiol. Lung Cell. Mol. Physiol. 300, L25–L31 (2011).
Hill, D. B. & Button, B. in Mucins: Strategies 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. Environment friendly supply of RNA interference oligonucleotides to polarized airway epithelia in vitro. Am. J. Physiol. Lung Cell. Mol. Physiol. 305, L23–L32 (2013).
Krishnamurthy, S. et al. Manipulation of cell physiology allows gene silencing in well-differentiated airway epithelia. Mol. Ther. Nucleic Acids 1, e41 (2012).
Burgel, P.-R., Montani, D., Danel, C., Dusser, D. J. & Nadel, J. A. A morphometric research of mucins and small airway plugging in cystic fibrosis. Thorax 62, 153–161 (2007).
Ratjen, F. Cystic fibrosis: the function of the small airways. J. Aerosol Med. Pulm. Drug Deliv. 25, 261–264 (2012).
van den Berge, M., ten Hacken, N. H. T., Cohen, J., Douma, W. R. & Postma, D. S. Small airway illness in bronchial asthma and COPD: scientific implications. Chest 139, 412–423 (2011).
Tiddens, H. A. W. M., Donaldson, S. H., Rosenfeld, M. & Paré, P. D. Cystic fibrosis lung illness begins within the small airways: can we deal with it extra successfully? Pediatr. Pulmonol. 45, 107–117 (2010).
Tatsuta, M. et al. Results of cigarette smoke on barrier perform and tight junction proteins within the bronchial epithelium: protecting function of cathelicidin LL-37. Respir. Res. 20, 251 (2019).
Maeki, M., Uno, S., Niwa, A., Okada, Y. & Tokeshi, M. Microfluidic applied sciences and gadgets for lipid nanoparticle-based RNA supply. J. Management. Launch 344, 80–96 (2022).
Cheng, M. H. Y. et al. Induction of bleb buildings in lipid nanoparticle formulations of mRNA results in improved transfection efficiency. 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).
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).
Kulkarni, J. A. et al. Fusion-dependent formation of lipid nanoparticles containing macromolecular payloads. Nanoscale 11, 9023–9031 (2019).
Richardson, S. J., Bai, A., Kulkarni, A. A. & Moghaddam, M. F. Effectivity in drug discovery: liver S9 fraction assay as a display screen for metabolic stability. Drug Metab. Lett. 10, 83–90 (2016).
Scholte, B. J., Davidson, D. J., Wilke, M. & de Jonge, H. R. Animal fashions of cystic fibrosis. J. Cyst. Fibros. 3, 183–190 (2004).
McCarron, A., Donnelley, M. & Parsons, D. Airway illness phenotypes in animal fashions of cystic fibrosis. Respir. Res. 19, 54 (2018).
Kim, N. et al. Inhaled gene remedy of preclinical muco-obstructive lung ailments by nanoparticles able to breaching the airway mucus barrier. Thorax 77, 812–820 (2022).
Phillips, J. E., Zhang, X. & Johnston, J. A. Dry powder and nebulized aerosol inhalation of prescribed drugs delivered to mice utilizing a nose-only publicity system. J. Vis. Exp. https://doi.org/10.3791/55454 (2017).
Beck, S. E. et al. Deposition and expression of aerosolized rAAV vectors within the lungs of rhesus macaques. Mol. Ther. 6, 546–554 (2002).
Woo, C. J. et al. Inhaled supply of a lipid nanoparticle encapsulated messenger RNA encoding a ciliary protein for the remedy of major ciliary dyskinesia. Pulm. Pharmacol. Ther. 75, 102134 (2022).
Okuda, Okay. et al. Secretory cells dominate airway CFTR expression and performance in human airway superficial epithelia. Am. J. Respir. Crit. Care Med. 203, 1275–1289 (2021).
Carraro, G. et al. Transcriptional evaluation of cystic fibrosis airways at single-cell decision reveals altered epithelial cell states and composition. Nat. Med. 27, 806–814 (2021).
Hodges, C. A. & Conlon, R. A. Delivering on the promise of gene enhancing for cystic fibrosis. Genes Dis. 6, 97–108 (2019).
Vanover, D. et al. Nebulized mRNA-encoded antibodies defend hamsters from SARS-CoV-2 an infection. Adv. Sci. 9, 2202771 (2022).
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 supply. Nat. Biomed. Eng. 7, 901–910 (2023).
Chen, D. et al. Fast discovery of potent siRNA-containing lipid nanoparticles enabled by managed microfluidic formulation. J. Am. Chem. Soc. 134, 6948–6951 (2012).
Heyes, J., Palmer, L., Bremner, Okay. & MacLachlan, I. Cationic lipid saturation influences intracellular supply of encapsulated nucleic acids. J. Management. Launch 107, 276–287 (2005).