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 enhancing 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 enhancing. Nat. Biotechnol. 38, 845–855 (2020).
Poon, W., Kingston, B. R., Ouyang, B., Ngo, W. & Chan, W. C. W. A framework for designing supply programs. Nat. Nanotechnol. 15, 819–829 (2020). This Overview completely discusses the traits of NPs required for efficient supply inside a organic context.
Patel, S. et al. Transient 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 extend the circulation time of liposomes. FEBS Lett. 268, 235–237 (1990).
Witzigmann, D. et al. Lipid nanoparticle know-how 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 examine found that the ApoE–LDLR pathway facilitates hepatocyte transfection when LNPs comprise 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 enhancing 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 in opposition to 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. Easy methods to deal with 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 lively particles manufactured by way of 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 examine explored the applying of polymeric NPs for inhaled mRNA supply, highlighting the potential benefit of polymers for nebulization by means of their self-assembly.
Kalra, H. et al. Vesiclepedia: a compendium for extracellular vesicles with steady neighborhood 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 by way of 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 may be pseudotyped for mRNA supply. Science 373, 882–889 (2021).
Elsharkasy, O. M. et al. Extracellular vesicles as drug supply programs: 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 techniques 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 means of 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 enhancing 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 examine (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 complicated for in vivo genome enhancing. Nat. Nanotechnol. 14, 974–980 (2019).
Mirjalili Mohanna, S. Z. et al. LNP-mediated supply of CRISPR RNP for wide-spread in vivo genome enhancing 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 ample 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 concentrating on (SORT) nanoparticles for tissue-specific mRNA supply and CRISPR–Cas gene enhancing. Nat. Nanotechnol. 15, 313–320 (2020). This groundbreaking examine discovered that incorporating otherwise charged (SORT) lipids into the traditional four-component LNPs shifts the placement 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 concentrating on nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021). This work completely investigated the impression of SORT lipids added to LNPs on the formation of the biomolecular corona on the NP floor and its function in attaining 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 means of 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 primarily based 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 enhancing. 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 transforming. 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. Customized 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. Rules 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 enhancing. 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‐primarily based 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 dwelling animals. Proc. Natl Acad. Sci. USA 114, E448–E456 (2017).
Ben-Akiva, E. et al. Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free concentrating 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 concentrating 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 by way of PET–CT and near-infrared imaging. Nat. Biomed. Eng. 3, 371–380 (2019). This pioneering examine 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 concentrating 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. Customized RNA mutanome vaccines mobilize poly-specific therapeutic immunity in opposition to 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 centered 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 decreasing 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 means of intravenous injection. Sci. Adv. 6, eabb4429 (2020). This examine 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 enormous 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 enhancing for sickle cell illness and β-thalassemia. N. Engl. J. Med. 384, 252–260 (2021).
Hirabayashi, H. & Fujisaki, J. Bone-specific drug supply programs: approaches by way of 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 examine proposes that bettering 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 concentrating 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 by way of 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 concentrating 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 by way of 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’ve got 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 programs. 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 examine reveals the potential for supply of mRNA-loaded PBAE NPs on to the submucosa of the abdomen utilizing orally ingested robotic drugs.
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 concentrating on microRNA-132 in sufferers with coronary heart failure: outcomes of a first-in-human section 1b randomized, double-blind, placebo-controlled examine. Eur. Coronary heart J. 42, 178–188 (2021).
Nishiyama, T. et al. Exact genomic enhancing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Sci. Transl. Med. 14, eade1633 (2022).
Reichart, D. et al. Environment friendly in vivo genome enhancing prevents hypertrophic cardiomyopathy in mice. Nat. Med. 29, 412–421 (2023).
Chai, A. C. et al. Base enhancing 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. Current advances in nanotechnology-based drug supply programs 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 in opposition to 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 enhancing. Nat. Commun. 9, 2481 (2018). This examine presents in utero gene enhancing 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. Current 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 means of Hes1 modulation with siRNA nanoparticles in grownup guinea pigs. Mol. Ther. 26, 1313–1326 (2018).
Gao, X. et al. Therapy of autosomal dominant listening to loss by in vivo supply of genome enhancing brokers. Nature 553, 217–221 (2018).
Jero, J. et al. Cochlear gene supply by means of an intact spherical window membrane in mouse. Hum. Gene Ther. 12, 539–548 (2001).
Egeblad, M., Nakasone, E. S. & Werb, Z. Tumors as organs: complicated tissues that interface with your complete 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 programs to strong tumor micromilieu: previous, current, and future views. ACS Nano 12, 10636–10664 (2018).
Hansen, A. E. et al. Positron emission tomography primarily based elucidation of the improved permeability and retention impact in canines 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 strong 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 strong tumour.
Schroeder, A. et al. Treating metastatic most cancers with nanotechnology. Nat. Rev. Most cancers 12, 39–50 (2012).
Chan, W. C. W. Rules of nanoparticle supply to strong 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 surroundings surrounding NPs and their physicochemical attributes.
Kingston, B. R. et al. Particular endothelial cells govern nanoparticle entry into strong 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 determine a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo. J. Management. Launch 357, 394–403 (2023).
Vetter, V. C. & Wagner, E. Focusing on nucleic acid-based therapeutics to tumors: challenges and techniques for polyplexes. J. Management. Launch 346, 110–135 (2022).
Yong, S. et al. Twin‐focused lipid nanotherapeutic increase 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 examine 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, guaranteeing 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 practical 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 Resolution. 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 practical 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 function of pulmonary surfactant in siRNA inhalation remedy. J. Management. Launch 220, 642–650 (2015).
