Zhang, Y.-N., Poon, W., Tavares, A. J., McGilvray, I. D. & Chan, W. C. W. Nanoparticle–liver interactions: mobile uptake and hepatobiliary elimination. J. Management. Launch 240, 332–348 (2016).
Akinc, A. et al. The Onpattro story and the medical translation of nanomedicines containing nucleic acid-based medicine. Nat. Nanotechnol. 14, 1084–1087 (2019).
Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene modifying for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).
Rotolo, L. et al. Species-agnostic polymeric formulations for inhalable messenger RNA supply to the lung. Nat. Mater. 22, 369–379 (2023).
Zhong, R. et al. Hydrogels for RNA supply. Nat. Mater. 22, 818–831 (2023).
Van Haasteren, J. et al. The supply problem: fulfilling the promise of therapeutic genome modifying. Nat. Biotechnol. 38, 845–855 (2020).
Poon, W., Kingston, B. R., Ouyang, B., Ngo, W. & Chan, W. C. W. A framework for designing supply techniques. Nat. Nanotechnol. 15, 819–829 (2020). This Overview totally discusses the traits of NPs required for efficient supply inside a organic context.
Patel, S. et al. Temporary replace on endocytosis of nanomedicines. Adv. Drug Deliv. Rev. 144, 90–111 (2019).
Alameh, M.-G. et al. Lipid nanoparticles improve the efficacy of mRNA and protein subunit vaccines by inducing strong T follicular helper cell and humoral responses. Immunity 54, 2877–2892.e7 (2021).
Han, X. et al. Adjuvant lipidoid-substituted lipid nanoparticles increase the immunogenicity of SARS-CoV-2 mRNA vaccines. Nat. Nanotechnol. 18, 1105–1114 (2023).
Tsoi, Okay. M. et al. Mechanism of hard-nanomaterial clearance by the liver. Nat. Mater. 15, 1212–1221 (2016).
Klibanov, A. L., Maruyama, Okay., Torchilin, V. P. & Huang, L. Amphipathic polyethyleneglycols successfully lengthen the circulation time of liposomes. FEBS Lett. 268, 235–237 (1990).
Witzigmann, D. et al. Lipid nanoparticle expertise for therapeutic gene regulation within the liver. Adv. Drug Deliv. Rev. 159, 344–363 (2020).
Akinc, A. et al. Focused supply of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18, 1357–1364 (2010). This research found that the ApoE–LDLR pathway facilitates hepatocyte transfection when LNPs include ionizable cationic lipids however not when completely cationic lipids are used.
Nair, J. Okay. et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits strong RNAi-mediated gene silencing. J. Am. Chem. Soc. 136, 16958–16961 (2014).
Kasiewicz, L. N. et al. GalNAc–lipid nanoparticles allow non-LDLR dependent hepatic supply of a CRISPR base modifying remedy. Nat. Commun. 14, 2776 (2023).
Ozelo, M. C. et al. Valoctocogene roxaparvovec gene remedy for hemophilia A. N. Engl. J. Med. 386, 1013–1025 (2022).
Sato, Y. et al. Decision of liver cirrhosis utilizing vitamin A-coupled liposomes to ship siRNA towards a collagen-specific chaperone. Nat. Biotechnol. 26, 431–442 (2008).
Lawitz, E. J. et al. BMS‐986263 in sufferers with superior hepatic fibrosis: 36‐week outcomes from a randomized, placebo‐managed section 2 trial. Hepatology 75, 912–923 (2022).
Han, X. et al. Ligand-tethered lipid nanoparticles for focused RNA supply to deal with liver fibrosis. Nat. Commun. 14, 75 (2023).
Paunovska, Okay. et al. Nanoparticles containing oxidized ldl cholesterol ship mrna to the liver microenvironment at clinically related doses. Adv. Mater. 31, 1807748 (2019).
Eygeris, Y., Gupta, M., Kim, J. & Sahay, G. Chemistry of lipid nanoparticles for RNA supply. Acc. Chem. Res. 55, 2–12 (2022).
Zhang, Y., Solar, C., Wang, C., Jankovic, Okay. E. & Dong, Y. Lipids and lipid derivatives for RNA supply. Chem. Rev. 121, 12181–12277 (2021).
Viger-Gravel, J. et al. Construction of lipid nanoparticles containing sirna or mrna by dynamic nuclear polarization-enhanced NMR spectroscopy. J. Phys. Chem. B 122, 2073–2081 (2018).
Goula, D. et al. Polyethylenimine-based intravenous supply of transgenes to mouse lung. Gene Ther. 5, 1291–1295 (1998).
Inexperienced, J. J., Langer, R. & Anderson, D. G. A combinatorial polymer library method yields perception into nonviral gene supply. Acc. Chem. Res. 41, 749–759 (2008).
Joubert, F. et al. Exact and systematic finish group chemistry modifications on PAMAM and poly(l-lysine) dendrimers to enhance cytosolic supply of mRNA. J. Management. Launch 356, 580–594 (2023).
Yang, W., Mixich, L., Boonstra, E. & Cabral, H. Polymer-based mRNA supply methods for superior therapies. Adv. Healthc. Mater. 12, 2202688 (2023).
Cabral, H., Miyata, Okay., Osada, Okay. & Kataoka, Okay. Block copolymer micelles in nanomedicine functions. Chem. Rev. 118, 6844–6892 (2018).
He, D. & Wagner, E. Outlined polymeric supplies for gene supply. Macromol. Biosci. 15, 600–612 (2015).
Reinhard, S. & Wagner, E. Tips on how to sort out the problem of siRNA supply with sequence-defined oligoamino amides. Macromol. Biosci. 17, 1600152 (2017).
DeSimone, J. M. Co-opting Moore’s legislation: therapeutics, vaccines and interfacially energetic particles manufactured through PRINT®. J. Management. Launch 240, 541–543 (2016).
Patel, A. Okay. et al. Inhaled nanoformulated mRNA polyplexes for protein manufacturing in lung epithelium. Adv. Mater. 31, 1805116 (2019). This research explored the appliance of polymeric NPs for inhaled mRNA supply, highlighting the potential benefit of polymers for nebulization by their self-assembly.
Kalra, H. et al. Vesiclepedia: a compendium for extracellular vesicles with steady group annotation. PLoS Biol. 10, e1001450 (2012).
Wahlgren, J. et al. Plasma exosomes can ship exogenous brief interfering RNA to monocytes and lymphocytes. Nucleic Acids Res. 40, e130–e130 (2012).
Alvarez-Erviti, L. et al. Supply of siRNA to the mouse mind by systemic injection of focused exosomes. Nat. Biotechnol. 29, 341–345 (2011).
Ståhl, A. et al. A novel mechanism of bacterial toxin switch inside host blood cell-derived microvesicles. PLoS Pathog. 11, e1004619 (2015).
Melamed, J. R. et al. Ionizable lipid nanoparticles ship mRNA to pancreatic β cells through macrophage-mediated gene switch. Sci. Adv. 9, eade1444 (2023).
Wang, Q. et al. ARMMs as a flexible platform for intracellular supply of macromolecules. Nat. Commun. 9, 960 (2018).
Segel, M. et al. Mammalian retrovirus-like protein PEG10 packages its personal mRNA and will be pseudotyped for mRNA supply. Science 373, 882–889 (2021).
Elsharkasy, O. M. et al. Extracellular vesicles as drug supply techniques: why and the way? Adv. Drug Deliv. Rev. 159, 332–343 (2020).
Klein, D. et al. Centyrin ligands for extrahepatic supply of siRNA. Mol. Ther. 29, 2053–2066 (2021).
Brown, Okay. M. et al. Increasing RNAi therapeutics to extrahepatic tissues with lipophilic conjugates. Nat. Biotechnol. 40, 1500–1508 (2022).
Wels, M., Roels, D., Raemdonck, Okay., De Smedt, S. C. & Sauvage, F. Challenges and methods for the supply of biologics to the cornea. J. Management. Launch 333, 560–578 (2021).
Baran-Rachwalska, P. et al. Topical siRNA supply to the cornea and anterior eye by hybrid silicon-lipid nanoparticles. J. Management. Launch 326, 192–202 (2020).
Bogaert, B. et al. A lipid nanoparticle platform for mRNA supply by repurposing of cationic amphiphilic medicine. J. Management. Launch 350, 256–270 (2022).
Kim, H. M. & Woo, S. J. Ocular drug supply to the retina: present improvements and future views. Pharmaceutics 13, 108 (2021).
Yiu, G. et al. Suprachoroidal and subretinal injections of AAV utilizing transscleral microneedles for retinal gene supply in nonhuman primates. Mol. Ther. Strategies Clin. Dev. 16, 179–191 (2020).
Weng, C. Y. Bilateral subretinal voretigene neparvovec-rzyl (Luxturna) gene remedy. Ophthalmol. Retin. 3, 450 (2019).
Jaskolka, M. C. et al. Exploratory security profile of EDIT-101, a first-in-human in vivo CRISPR gene modifying remedy for CEP290-related retinal degeneration. Make investments. Ophthalmol. Vis. Sci. 63, 2836–A0352 (2022).
Chirco, Okay. R., Martinez, C. & Lamba, D. A. Developments in pre-clinical improvement of gene editing-based therapies to deal with inherited retinal ailments. Vis. Res. 209, 108257 (2023).
Leroy, B. P. et al. Efficacy and security of sepofarsen, an intravitreal RNA antisense oligonucleotide, for the remedy of CEP290-associated Leber congenital amaurosis (LCA10): a randomized, double-masked, sham-controlled, section 3 research (ILLUMINATE). Make investments. Ophthalmol. Vis. Sci. 63, 4536-F0323 (2022).
Ammar, M. J., Hsu, J., Chiang, A., Ho, A. C. & Regillo, C. D. Age-related macular degeneration remedy: a assessment. Curr. Opin. Ophthalmol. 31, 215–221 (2020).
Goldberg, R. et al. Efficacy of intravitreal pegcetacoplan in sufferers with geographic atrophy (GA): 12-month outcomes from the section 3 OAKS and DERBY research. Make investments. Ophthalmol. Vis. Sci. 63, 1500–1500 (2022).
Shen, J. et al. Suprachoroidal gene switch with nonviral nanoparticles. Sci. Adv. 6, eaba1606 (2020).
Tan, G. et al. A core-shell nanoplatform as a nonviral vector for focused supply of genes to the retina. Acta Biomater. 134, 605–620 (2021).
Jin, J. et al. Anti-inflammatory and antiangiogenic results of nanoparticle-mediated supply of a pure angiogenic inhibitor. Investig. Opthalmol. Vis. Sci. 52, 6230 (2011).
Keenan, T. D. L., Cukras, C. A. & Chew, E. Y. Age-related macular degeneration: epidemiology and medical features. Adv. Exp. Med. Biol. 1256, 1–31 (2021).
Chen, G. et al. A biodegradable nanocapsule delivers a Cas9 ribonucleoprotein advanced for in vivo genome modifying. Nat. Nanotechnol. 14, 974–980 (2019).
Mirjalili Mohanna, S. Z. et al. LNP-mediated supply of CRISPR RNP for wide-spread in vivo genome modifying in mouse cornea. J. Management. Launch 350, 401–413 (2022).
Patel, S., Ryals, R. C., Weller, Okay. Okay., Pennesi, M. E. & Sahay, G. Lipid nanoparticles for supply of messenger RNA to the again of the attention. J. Management. Launch 303, 91–100 (2019).
Solar, D. et al. Non-viral gene remedy for stargardt illness with ECO/pRHO-ABCA4 self-assembled nanoparticles. Mol. Ther. 28, 293–303 (2020).
Herrera-Barrera, M. et al. Peptide-guided lipid nanoparticles ship mRNA to the neural retina of rodents and nonhuman primates. Sci. Adv. 9, eadd4623 (2023).
Huertas, A. et al. Pulmonary vascular endothelium: the orchestra conductor in respiratory ailments: highlights from fundamental analysis to remedy. Eur. Respir. J. 51, 1700745 (2018).
Hong, Okay.-H. et al. Genetic ablation of the Bmpr2 gene in pulmonary endothelium is enough to predispose to pulmonary arterial hypertension. Circulation 118, 722–730 (2008).
Dahlman, J. E. et al. In vivo endothelial siRNA supply utilizing polymeric nanoparticles with low molecular weight. Nat. Nanotechnol. 9, 648–655 (2014).
Cheng, Q. et al. Selective organ focusing on (SORT) nanoparticles for tissue-specific mRNA supply and CRISPR–Cas gene modifying. Nat. Nanotechnol. 15, 313–320 (2020). This groundbreaking research discovered that incorporating otherwise charged (SORT) lipids into the traditional four-component LNPs shifts the situation of mRNA transfection among the many liver, spleen and lungs.
Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA supply by selective organ focusing on nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021). This work totally investigated the affect of SORT lipids added to LNPs on the formation of the biomolecular corona on the NP floor and its position in reaching organ-specific transfection.
Kimura, S. & Harashima, H. On the mechanism of tissue-selective gene supply by lipid nanoparticles. J. Management. Launch https://doi.org/10.1016/j.jconrel.2023.03.052 (2023).
Qiu, M. et al. Lung-selective mRNA supply of artificial lipid nanoparticles for the remedy of pulmonary lymphangioleiomyomatosis. Proc. Natl Acad. Sci. USA 119, e2116271119 (2022).
Kaczmarek, J. C. et al. Polymer–lipid nanoparticles for systemic supply of mRNA to the lungs. Angew. Chem. Int. Ed. 55, 13808–13812 (2016).
Shen, A. M. & Minko, T. Pharmacokinetics of inhaled nanotherapeutics for pulmonary supply. J. Management. Launch 326, 222–244 (2020).
Alton, E. W. F. W. et al. Repeated nebulisation of non-viral CFTR gene remedy in sufferers with cystic fibrosis: a randomised, double-blind, placebo-controlled, section 2b trial. Lancet Respir. Med. 3, 684–691 (2015).
Kim, J. et al. Engineering lipid nanoparticles for enhanced intracellular supply of mRNA by inhalation. ACS Nano 16, 14792–14806 (2022).
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).
Qiu, Y. et al. Efficient mRNA pulmonary supply by dry powder formulation of PEGylated artificial KL4 peptide. J. Management. Launch 314, 102–115 (2019).
Popowski, Okay. D. et al. Inhalable dry powder mRNA vaccines based mostly on extracellular vesicles. Matter 5, 2960–2974 (2022).
Telko, M. J. & Hickey, A. J. Dry powder inhaler formulation. Respir. Care 50, 1209 (2005).
Li, B. et al. Combinatorial design of nanoparticles for pulmonary mRNA supply and genome modifying. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01679-x (2023).
Fahy, J. V. & Dickey, B. F. Airway mucus operate and dysfunction. N. Engl. J. Med. 363, 2233–2247 (2010).
Schneider, C. S. et al. Nanoparticles that don’t adhere to mucus present uniform and long-lasting drug supply to airways following inhalation. Sci. Adv. 3, e1601556 (2017).
Wang, J. et al. Pulmonary surfactant–biomimetic nanoparticles potentiate heterosubtypic influenza immunity. Science 367, eaau0810 (2020).
Rock, J. R., Randell, S. H. & Hogan, B. L. M. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and reworking. Dis. Mannequin. Mech. 3, 545–556 (2010).
Getts, D. R. et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat. Biotechnol. 30, 1217–1224 (2012).
Leuschner, F. et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat. Biotechnol. 29, 1005–1010 (2011).
Rojas, L. A. et al. Personalised RNA neoantigen vaccines stimulate T cells in pancreatic most cancers. Nature 618, 144–150 (2023).
Bevers, S. et al. mRNA–LNP vaccines tuned for systemic immunization induce sturdy antitumor immunity by participating splenic immune cells. Mol. Ther. 30, 3078–3094 (2022).
Blanco, E., Shen, H. & Ferrari, M. Ideas of nanoparticle design for overcoming organic obstacles to drug supply. Nat. Biotechnol. 33, 941–951 (2015).
Kranz, L. M. et al. Systemic RNA supply to dendritic cells exploits antiviral defence for most cancers immunotherapy. Nature 534, 396–401 (2016).
Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA supply and CRISPR–Cas gene modifying. Nat. Mater. 20, 701–710 (2021).
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).
Zhao, X. et al. Imidazole‐based mostly artificial lipidoids for in vivo mRNA supply into major T lymphocytes. Angew. Chem. Int. Ed. 59, 20083–20089 (2020).
LoPresti, S. T., Arral, M. L., Chaudhary, N. & Whitehead, Okay. A. The substitute of helper lipids with charged alternate options in lipid nanoparticles facilitates focused mRNA supply to the spleen and lungs. J. Management. Launch 345, 819–831 (2022).
McKinlay, C. J., Benner, N. L., Haabeth, O. A., Waymouth, R. M. & Wender, P. A. Enhanced mRNA supply into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters. Proc. Natl Acad. Sci. USA 115, E5859–E5866 (2018).
McKinlay, C. J. et al. Cost-altering releasable transporters (CARTs) for the supply and launch of mRNA in residing animals. Proc. Natl Acad. Sci. USA 114, E448–E456 (2017).
Ben-Akiva, E. et al. Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free focusing on of splenic dendritic cells for most cancers vaccination. Proc. Natl Acad. Sci. USA 120, e2301606120 (2023).
Tombácz, I. et al. Extremely environment friendly CD4+ T cell focusing on and genetic recombination utilizing engineered CD4+ cell-homing mRNA–LNPs. Mol. Ther. 29, 3293–3304 (2021).
Rurik, J. G. et al. CAR T cells produced in vivo to deal with cardiac damage. Science 375, 91–96 (2022).
Kim, J., Eygeris, Y., Gupta, M. & Sahay, G. Self-assembled mRNA vaccines. Adv. Drug Deliv. Rev. 170, 83–112 (2021).
Lindsay, Okay. E. et al. Visualization of early occasions in mRNA vaccine supply in non-human primates through PET–CT and near-infrared imaging. Nat. Biomed. Eng. 3, 371–380 (2019). This pioneering research delved into the biodistribution of lipid-based mRNA vaccines after their intramuscular injection into non-human primates utilizing a twin radionuclide–near-infrared probe.
Alberer, M. et al. Security and immunogenicity of a mRNA rabies vaccine in wholesome adults: an open-label, non-randomised, potential, first-in-human section 1 medical trial. Lancet 390, 1511–1520 (2017).
Evaluation Report: Comirnaty EMA/707383/2020 (European Medicines Company, 2021); https://www.ema.europa.eu/en/paperwork/assessment-report/comirnaty-epar-public-assessment-report_en.pdf
Evaluation Report: COVID-19 Vaccine Moderna EMA/15689/2021 (European Medicines Company, 2021); https://www.ema.europa.eu/en/paperwork/assessment-report/spikevax-previously-covid-19-vaccine-moderna-epar-public-assessment-report_en.pdf
Ke, X. et al. Bodily and chemical profiles of nanoparticles for lymphatic focusing on. Adv. Drug Deliv. Rev. 151–152, 72–93 (2019).
Hansen, Okay. C., D’Alessandro, A., Clement, C. C. & Santambrogio, L. Lymph formation, composition and circulation: a proteomics perspective. Int. Immunol. 27, 219–227 (2015).
Chen, J. et al. Lipid nanoparticle-mediated lymph node-targeting supply of mRNA most cancers vaccine elicits strong CD8+ T cell response. Proc. Natl Acad. Sci. USA 119, e2207841119 (2022).
Liu, S. et al. Zwitterionic phospholipidation of cationic polymers facilitates systemic mRNA supply to spleen and lymph nodes. J. Am. Chem. Soc. 143, 21321–21330 (2021).
Sahin, U. et al. Personalised RNA mutanome vaccines mobilize poly-specific therapeutic immunity towards most cancers. Nature 547, 222–226 (2017).
Kreiter, S. et al. Intranodal vaccination with bare antigen-encoding rna elicits potent prophylactic and therapeutic antitumoral immunity. Most cancers Res. 70, 9031–9040 (2010).
Fan, C.-H. et al. Folate-conjugated gene-carrying microbubbles with targeted ultrasound for concurrent blood–mind barrier opening and native gene supply. Biomaterials 106, 46–57 (2016).
Yu, Y. J. et al. Boosting mind uptake of a therapeutic antibody by lowering its affinity for a transcytosis goal. Sci. Transl. Med. 3, 84ra44 (2011).
Yu, Y. J. et al. Therapeutic bispecific antibodies cross the blood–mind barrier in nonhuman primates. Sci. Transl. Med. 6, 261ra154 (2014).
Kariolis, M. S. et al. Mind supply of therapeutic proteins utilizing an Fc fragment blood–mind barrier transport automobile in mice and monkeys. Sci. Transl. Med. 12, eaay1359 (2020).
Ullman, J. C. et al. Mind supply and exercise of a lysosomal enzyme utilizing a blood–mind barrier transport automobile in mice. Sci. Transl. Med. 12, eaay1163 (2020).
Ma, F. et al. Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced mind supply by intravenous injection. Sci. Adv. 6, eabb4429 (2020). This research means that designing lipids to imitate neurotransmitters and incorporating them into NPs can improve the supply of nucleic acids and proteins to the mind following IV injection.
Zhou, Y. et al. Blood–mind barrier-penetrating siRNA nanomedicine for Alzheimer’s illness remedy. Sci. Adv. 6, eabc7031 (2020).
Li, W. et al. BBB pathophysiology-independent supply of siRNA in traumatic mind damage. Sci. Adv. 7, eabd6889 (2021).
Nance, E. A. et al. A dense poly(ethylene glycol) coating improves penetration of huge polymeric nanoparticles inside mind tissue. Sci. Transl. Med. 4, 149ra119 (2012).
Thorne, R. G. & Nicholson, C. In vivo diffusion evaluation with quantum dots and dextrans predicts the width of mind extracellular area. Proc. Natl Acad. Sci. USA 103, 5567–5572 (2006).
Kim, M. et al. Supply of self-replicating messenger RNA into the mind for the remedy of ischemic stroke. J. Management. Launch 350, 471–485 (2022).
Willerth, S. M. & Sakiyama-Elbert, S. E. Approaches to neural tissue engineering utilizing scaffolds for drug supply. Adv. Drug Deliv. Rev. 59, 325–338 (2007).
Saucier-Sawyer, J. Okay. et al. Distribution of polymer nanoparticles by convection-enhanced supply to mind tumors. J. Management. Launch 232, 103–112 (2016).
Dhaliwal, H. Okay., Fan, Y., Kim, J. & Amiji, M. M. Intranasal supply and transfection of mRNA therapeutics within the mind utilizing cationic liposomes. Mol. Pharm. 17, 1996–2005 (2020).
Frangoul, H. et al. CRISPR–Cas9 gene modifying for sickle cell illness and β-thalassemia. N. Engl. J. Med. 384, 252–260 (2021).
Hirabayashi, H. & Fujisaki, J. Bone-specific drug supply techniques: approaches through chemical modification of bone-seeking brokers. Clin. Pharmacokinet. 42, 1319–1330 (2003).
Wang, G., Mostafa, N. Z., Incani, V., Kucharski, C. & Uludağ, H. Bisphosphonate-decorated lipid nanoparticles designed as drug carriers for bone ailments. J. Biomed. Mater. Res. A 100, 684–693 (2012).
Giger, E. V. et al. Gene supply with bisphosphonate-stabilized calcium phosphate nanoparticles. J. Management. Launch 150, 87–93 (2011).
Xue, L. et al. Rational design of bisphosphonate lipid-like supplies for mRNA supply to the bone microenvironment. J. Am. Chem. Soc. 144, 9926–9937 (2022). This research proposes that enhancing lipid design to imitate bisphosphates can enhance LNP-mediated mRNA supply to the bone microenvironment after IV injection.
Liang, C. et al. Aptamer-functionalized lipid nanoparticles focusing on osteoblasts as a novel RNA interference-based bone anabolic technique. Nat. Med. 21, 288–294 (2015).
Zhang, Y., Wei, L., Miron, R. J., Shi, B. & Bian, Z. Anabolic bone formation through a site-specific bone-targeting supply system by interfering with semaphorin 4D expression. J. Bone Miner. Res. 30, 286–296 (2015).
Zhang, G. et al. A supply system focusing on bone formation surfaces to facilitate RNAi-based anabolic remedy. Nat. Med. 18, 307–314 (2012).
Shi, D., Toyonaga, S. & Anderson, D. G. In vivo RNA supply to hematopoietic stem and progenitor cells through focused lipid nanoparticles. Nano Lett. 23, 2938–2944 (2023).
Sago, C. D. et al. Nanoparticles that ship RNA to bone marrow recognized by in vivo directed evolution. J. Am. Chem. Soc. 140, 17095–17105 (2018).
Zhang, X., Li, Y., Chen, Y. E., Chen, J. & Ma, P. X. Cell-free 3D scaffold with two-stage supply of miRNA-26a to regenerate critical-sized bone defects. Nat. Commun. 7, 10376 (2016).
Wang, P. et al. In vivo bone tissue induction by freeze-dried collagen–nanohydroxyapatite matrix loaded with BMP2/NS1 mRNAs lipopolyplexes. J. Management. Launch 334, 188–200 (2021).
Athirasala, A. et al. Matrix stiffness regulates lipid nanoparticle-mRNA supply in cell-laden hydrogels. Nanomed. Nanotechnol. Biol. Med. 42, 102550 (2022).
Nims, R. J., Pferdehirt, L. & Guilak, F. Mechanogenetics: harnessing mechanobiology for mobile engineering. Curr. Opin. Biotechnol. 73, 374–379 (2022).
O’Driscoll, C. M., Bernkop-Schnürch, A., Friedl, J. D., Préat, V. & Jannin, V. Oral supply of non-viral nucleic acid-based therapeutics—do we now have the center for this? Eur. J. Pharm. Sci. 133, 190–204 (2019).
Ball, R. L., Bajaj, P. & Whitehead, Okay. A. Oral supply of siRNA lipid nanoparticles: destiny within the GI tract. Sci. Rep. 8, 2178 (2018).
Attarwala, H., Han, M., Kim, J. & Amiji, M. Oral nucleic acid remedy utilizing multi-compartmental supply techniques. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 10, e1478 (2018).
Abramson, A. et al. An ingestible self-orienting system for oral supply of macromolecules. Science 363, 611–615 (2019).
Abramson, A. et al. Oral mRNA supply utilizing capsule-mediated gastrointestinal tissue injections. Matter 5, 975–987 (2022). This research reveals the potential for supply of mRNA-loaded PBAE NPs on to the submucosa of the abdomen utilizing orally ingested robotic capsules.
Doll, S. et al. Area and cell-type resolved quantitative proteomic map of the human coronary heart. Nat. Commun. 8, 1469 (2017).
Xin, M., Olson, E. N. & Bassel-Duby, R. Mending damaged hearts: cardiac improvement as a foundation for grownup coronary heart regeneration and restore. Nat. Rev. Mol. Cell Biol. 14, 529–541 (2013).
Zangi, L. et al. Modified mRNA directs the destiny of coronary heart progenitor cells and induces vascular regeneration after myocardial infarction. Nat. Biotechnol. 31, 898–907 (2013).
Tang, R., Lengthy, T., Lui, Okay. O., Chen, Y. & Huang, Z.-P. A roadmap for fixing the guts: RNA regulatory networks in cardiac illness. Mol. Ther. Nucleic Acids 20, 673–686 (2020).
Han, P. et al. A protracted noncoding RNA protects the guts from pathological hypertrophy. Nature 514, 102–106 (2014).
Anttila, V. et al. Direct intramyocardial injection of VEGF mRNA in sufferers present process coronary artery bypass grafting. Mol. Ther. 31, 866–874 (2023).
Täubel, J. et al. Novel antisense remedy focusing on microRNA-132 in sufferers with coronary heart failure: outcomes of a first-in-human section 1b randomized, double-blind, placebo-controlled research. Eur. Coronary heart J. 42, 178–188 (2021).
Nishiyama, T. et al. Exact genomic modifying of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Sci. Transl. Med. 14, eade1633 (2022).
Reichart, D. et al. Environment friendly in vivo genome modifying prevents hypertrophic cardiomyopathy in mice. Nat. Med. 29, 412–421 (2023).
Chai, A. C. et al. Base modifying correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nat. Med. 29, 401–411 (2023).
Rubin, J. D. & Barry, M. A. Bettering molecular remedy within the kidney. Mol. Diagn. Ther. 24, 375–396 (2020).
Oroojalian, F. et al. Latest advances in nanotechnology-based drug supply techniques for the kidney. J. Management. Launch 321, 442–462 (2020).
Jiang, D. et al. DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney damage. Nat. Biomed. Eng. 2, 865–877 (2018).
Xu, Y. et al. NIR-II photoacoustic-active DNA origami nanoantenna for early analysis and good remedy of acute kidney damage. J. Am. Chem. Soc. 144, 23522–23533 (2022).
Stribley, J. M., Rehman, Okay. S., Niu, H. & Christman, G. M. Gene remedy and reproductive medication. Fertil. Steril. 77, 645–657 (2002).
Boekelheide, Okay. & Sigman, M. Is gene remedy for the remedy of male infertility possible? Nat. Clin. Pract. Urol. 5, 590–593 (2008).
Rodríguez-Gascón, A., del Pozo-Rodríguez, A., Isla, A. & Solinís, M. A. Vaginal gene remedy. Adv. Drug Deliv. Rev. 92, 71–83 (2015).
Lindsay, Okay. E. et al. Aerosol supply of artificial mRNA to vaginal mucosa results in sturdy expression of broadly neutralizing antibodies towards HIV. Mol. Ther. 28, 805–819 (2020).
Poley, M. et al. Nanoparticles accumulate within the feminine reproductive system throughout ovulation affecting most cancers remedy and fertility. ACS Nano 16, 5246–5257 (2022).
DeWeerdt, S. Prenatal gene remedy affords the earliest doable remedy. Nature 564, S6–S8 (2018).
Palanki, R., Peranteau, W. H. & Mitchell, M. J. Supply applied sciences for in utero gene remedy. Adv. Drug Deliv. Rev. 169, 51–62 (2021).
Riley, R. S. et al. Ionizable lipid nanoparticles for in utero mRNA supply. Sci. Adv. 7, 1028–1041 (2021).
Swingle, Okay. L. et al. Amniotic fluid stabilized lipid nanoparticles for in utero intra-amniotic mRNA supply. J. Management. Launch 341, 616–633 (2022).
Ricciardi, A. S. et al. In utero nanoparticle supply for site-specific genome modifying. Nat. Commun. 9, 2481 (2018). This research presents in utero gene modifying of a disease-causing β-thalassemia mutation in foetal mice.
Chaudhary, N. et al. Lipid nanoparticle construction and supply route throughout being pregnant dictates mRNA efficiency, immunogenicity, and well being within the mom and offspring. Preprint at bioRxiv https://doi.org/10.1101/2023.02.15.528720 (2023).
Younger, R. E. et al. Lipid nanoparticle composition drives mRNA supply to the placenta. Preprint at bioRxiv https://doi.org/10.1101/2022.12.22.521490 (2022).
Swingle, Okay. L. et al. Ionizable lipid nanoparticles for in vivo mRNA supply to the placenta throughout being pregnant. J. Am. Chem. Soc. 145, 4691–4706 (2023).
Lan, Y. et al. Latest improvement of AAV-based gene therapies for internal ear issues. Gene Ther. 27, 329–337 (2020).
Delmaghani, S. & El-Amraoui, A. Interior ear gene therapies take off: present guarantees and future challenges. J. Clin. Med. 9, 2309 (2020).
Wang, L., Kempton, J. B. & Brigande, J. V. Gene remedy in mouse fashions of deafness and stability dysfunction. Entrance. Mol. Neurosci. 11, 300 (2018).
Du, X. et al. Regeneration of cochlear hair cells and listening to restoration by Hes1 modulation with siRNA nanoparticles in grownup guinea pigs. Mol. Ther. 26, 1313–1326 (2018).
Gao, X. et al. Remedy of autosomal dominant listening to loss by in vivo supply of genome modifying brokers. Nature 553, 217–221 (2018).
Jero, J. et al. Cochlear gene supply by an intact spherical window membrane in mouse. Hum. Gene Ther. 12, 539–548 (2001).
Egeblad, M., Nakasone, E. S. & Werb, Z. Tumors as organs: advanced tissues that interface with the whole organism. Dev. Cell 18, 884–901 (2010).
El-Sawy, H. S., Al-Abd, A. M., Ahmed, T. A., El-Say, Okay. M. & Torchilin, V. P. Stimuli-responsive nano-architecture drug-delivery techniques to stable tumor micromilieu: previous, current, and future views. ACS Nano 12, 10636–10664 (2018).
Hansen, A. E. et al. Positron emission tomography based mostly elucidation of the improved permeability and retention impact in canine with most cancers utilizing copper-64 liposomes. ACS Nano 9, 6985–6995 (2015).
Zhou, Q. et al. Enzyme-activatable polymer–drug conjugate augments tumour penetration and remedy efficacy. Nat. Nanotechnol. 14, 799–809 (2019).
Sindhwani, S. et al. The entry of nanoparticles into stable tumours. Nat. Mater. 19, 566–575 (2020).
Wilhelm, S. et al. Evaluation of nanoparticle supply to tumours. Nat. Rev. Mater. 1, 16014 (2016). This Overview deeply explores the doable components behind the ineffective tumour-targeting of NPs, uncovering that solely a small fraction of the administered NP dose reaches a stable tumour.
Schroeder, A. et al. Treating metastatic most cancers with nanotechnology. Nat. Rev. Most cancers 12, 39–50 (2012).
Chan, W. C. W. Ideas of nanoparticle supply to stable tumors. BME Entrance. 4, 0016 (2023). This Overview delineates key ideas for designing tumour-targeting NPs, contemplating each macro- and micro-level evaluation of the atmosphere surrounding NPs and their physicochemical attributes.
Kingston, B. R. et al. Particular endothelial cells govern nanoparticle entry into stable tumors. ACS Nano 15, 14080–14094 (2021).
Boehnke, N. et al. Massively parallel pooled screening reveals genomic determinants of nanoparticle supply. Science 377, eabm5551 (2022).
Li, Y. et al. Multifunctional oncolytic nanoparticles ship self-replicating IL-12 RNA to eradicate established tumors and prime systemic immunity. Nat. Most cancers 1, 882–893 (2020).
Hotz, C. et al. Native supply of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication throughout a number of preclinical tumor fashions. Sci. Transl. Med. 13, eabc7804 (2021).
Li, W. et al. Biomimetic nanoparticles ship mRNAs encoding costimulatory receptors and improve T cell mediated most cancers immunotherapy. Nat. Commun. 12, 7264 (2021).
Van Lint, S. et al. Intratumoral supply of TriMix mRNA leads to T-cell activation by cross-presenting dendritic cells. Most cancers Immunol. Res. 4, 146–156 (2016).
Oberli, M. A. et al. Lipid nanoparticle assisted mRNA supply for potent most cancers immunotherapy. Nano Lett. 17, 1326–1335 (2017).
Huayamares, S. G. et al. Excessive-throughput screens establish a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo. J. Management. Launch 357, 394–403 (2023).
Vetter, V. C. & Wagner, E. Concentrating on nucleic acid-based therapeutics to tumors: challenges and methods for polyplexes. J. Management. Launch 346, 110–135 (2022).
Yong, S. et al. Twin‐focused lipid nanotherapeutic enhance for chemo‐immunotherapy of most cancers. Adv. Mater. 34, 2106350 (2022).
Kedmi, R. et al. A modular platform for focused RNAi therapeutics. Nat. Nanotechnol. 13, 214–219 (2018). This research developed a modular, ligand-based RNA supply platform that avoids the chemical conjugation of antibodies through the use of linkers that bind to the Fc area, making certain exact antibody orientation on the NP floor.
Mitchell, M. J. et al. Engineering precision nanoparticles for drug supply. Nat. Rev. Drug Discov. 20, 101–124 (2021).
Adachi, Okay., Enoki, T., Kawano, Y., Veraz, M. & Nakai, H. Drawing a high-resolution useful map of adeno-associated virus capsid by massively parallel sequencing. Nat. Commun. 5, 3075 (2014).
Dahlman, J. E. et al. Barcoded nanoparticles for top throughput in vivo discovery of focused therapeutics. Proc. Natl Acad. Sci. USA 114, 2060–2065 (2017). This work presents the outstanding capabilities of DNA barcoding and deep sequencing in conducting high-throughput screening of NPs, assessing their effectiveness in target-specific gene supply in vivo.
Da Silva Sanchez, A. J. et al. Common barcoding predicts in vivo ApoE-independent lipid nanoparticle supply. Nano Lett. 22, 4822–4830 (2022).
Guimaraes, P. P. G. et al. Ionizable lipid nanoparticles encapsulating barcoded mRNA for accelerated in vivo supply screening. J. Management. Launch 316, 404–417 (2019).
Dobrowolski, C. et al. Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA supply. Nat. Nanotechnol. 17, 871–879 (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).
Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Strategies 14, 865–868 (2017).
Keenum, M. C. et al. Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists. Biomaterials 297, 122097 (2023).
Grandi, F. C., Modi, H., Kampman, L. & Corces, M. R. Chromatin accessibility profiling by ATAC-seq. Nat. Protoc. 17, 1518–1552 (2022).
Rao, N., Clark, S. & Habern, O. Bridging genomics and tissue pathology: 10x Genomics explores new frontiers with the Visium Spatial Gene Expression Answer. Genet. Eng. Biotechnol. Information 40, 50–51 (2020).
Francia, V., Schiffelers, R. M., Cullis, P. R. & Witzigmann, D. The biomolecular corona of lipid nanoparticles for gene remedy. Bioconjug. Chem. 31, 2046–2059 (2020).
Shao, D. et al. HBFP: a brand new repository for human physique fluid proteome. Database 2021, baab065 (2021).
Greener, J. G., Kandathil, S. M., Moffat, L. & Jones, D. T. A information to machine studying for biologists. Nat. Rev. Mol. Cell Biol. 23, 40–55 (2022).
Zhang, H. et al. Algorithm for optimized mRNA design improves stability and immunogenicity. Nature 621, 396–403 (2023).
Wang, W. et al. Prediction of lipid nanoparticles for mRNA vaccines by the machine studying algorithm. Acta Pharm. Sin. B 12, 2950–2962 (2022).
Xu, Y. et al. AGILE platform: a deep learning-powered method to speed up LNP improvement for mRNA supply. Preprint at bioRxiv https://doi.org/10.1101/2023.06.01.543345 (2023). This work implements synthetic intelligence in ionizable lipid design for intramuscular mRNA supply.
Gong, D. et al. Machine studying guided construction operate predictions allow in silico nanoparticle screening for polymeric gene supply. Acta Biomater. 154, 349–358 (2022).
Reker, D. et al. Computationally guided high-throughput design of self-assembling drug nanoparticles. Nat. Nanotechnol. 16, 725–733 (2021).
Yamankurt, G. et al. Exploration of the nanomedicine-design area with high-throughput screening and machine studying. Nat. Biomed. Eng. 3, 318–327 (2019).
Lazarovits, J. et al. Supervised studying and mass spectrometry predicts the in vivo destiny of nanomaterials. ACS Nano 13, 8023–8034 (2019).
Goodfellow, I. et al. Generative adversarial networks. Commun. ACM 63, 139–144 (2020).
Repecka, D. et al. Increasing useful protein sequence areas utilizing generative adversarial networks. Nat. Mach. Intell. 3, 324–333 (2021).
De Backer, L., Cerrada, A., Pérez-Gil, J., De Smedt, S. C. & Raemdonck, Okay. Bio-inspired supplies in drug supply: exploring the position of pulmonary surfactant in siRNA inhalation remedy. J. Management. Launch 220, 642–650 (2015).