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Rev. 121, 12181 12277 \(2021\).\r:92)/F 4/H/N/Rect[447.574 377.77 452.168 367.59]/Subtype/Link/Type/Annot>> endobj 11 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:15. Zhang, Y., Sun, C., Wang, C., Jankovic, K. E. & Dong, Y. Lipids and lipid der\ ivatives for RNA delivery. Chem. Rev. 121, 12181 12277 \(2021\).\r:93)/F 4/H/N/Rect[511.63 345.52 516.223 335.34]/Subtype/Link/Type/Annot>> endobj 12 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:16. Tilcock, C. P. Lipid polymorphism. Chem. Phys. Lipids 40, 109 125 \(1986\).\ \r:94)/F 4/H/N/Rect[344.487 291.77 349.324 281.59]/Subtype/Link/Type/Annot>> endobj 13 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:16. Tilcock, C. P. Lipid polymorphism. Chem. Phys. Lipids 40, 109 125 \(1986\)\ .\r:95)/F 4/H/N/Rect[360.492 259.52 365.392 249.34]/Subtype/Link/Type/Annot>> endobj 14 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:13. Anselmo, A. C. & Mitragotri, S. Nanoparticles in the clinic: an update. Bioe\ ng. Transl. Med. 4, e10143 \(2019\).\r:96)/F 4/H/N/Rect[329.356 130.52 333.97 120.34]/Subtype/Link/Type/Annot>> endobj 15 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:17. Barenholz, Y. Doxil  the first FDA-approved nano-drug: lessons learned. J. \ Control. Rel. 160, 117 134 \(2012\).\r:97)/F 4/H/N/Rect[335.317 130.52 339.547 120.34]/Subtype/Link/Type/Annot>> endobj 16 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:17. Barenholz, Y. Doxil  the first FDA-approved nano-drug: lessons learned. J.\ Control. Rel. 160, 117 134 \(2012\).\r:98)/F 4/H/N/Rect[364.923 98.2704 369.219 88.0899]/Subtype/Link/Type/Annot>> endobj 17 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:22. Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nat. Rev. Ma\ ter. 1, 16014 \(2016\).\r:99)/F 4/H/N/Rect[371.796 98.2704 377.118 88.0899]/Subtype/Link/Type/Annot>> endobj 18 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:4. Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delive\ ry. Nat. Rev. Mater. 6, 1078 1094 \(2021\).\r:100)/F 4/H/N/Rect[456.416 66.0204 459.227 55.8399]/Subtype/Link/Type/Annot>> endobj 19 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:1. Yin, H. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15\ , 541 555 \(2014\).\r:71)/F 4/H/N/Rect[74.9613 539.02 77.0304 528.84]/Subtype/Link/Type/Annot>> endobj 20 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:2. Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N\ . Engl. \nJ. Med. 384, 403 416 \(2020\).\r:72)/F 4/H/N/Rect[203.603 485.27 206.251 475.09]/Subtype/Link/Type/Annot>> endobj 21 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:3. Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.\ N. Engl. \nJ. Med. 383, 2603 2615 \(2020\).\r:73)/F 4/H/N/Rect[207.589 485.27 210.189 475.09]/Subtype/Link/Type/Annot>> endobj 22 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:4. Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery.\ Nat. Rev. Mater. 6, 1078 1094 \(2021\).\r:74)/F 4/H/N/Rect[122.017 399.27 124.863 389.09]/Subtype/Link/Type/Annot>> endobj 23 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:4. Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery\ . Nat. Rev. Mater. 6, 1078 1094 \(2021\).\r:75)/F 4/H/N/Rect[151.094 377.77 153.925 367.59]/Subtype/Link/Type/Annot>> endobj 24 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:5. Anselmo, A. C. & Mitragotri, S. An overview of clinical and commercial impact o\ f drug delivery systems. J. Control. Rel. 190, 15 28 \(2014\).\r:76)/F 4/H/N/Rect[220.91 291.77 223.212 281.59]/Subtype/Link/Type/Annot>> endobj 25 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:6. Fenton, O. S., Olafson, K. N., Pillai, P. S., Mitchell, M. J. & Langer, R. Adva\ nces in biomaterials for drug delivery. Adv. Mater. https://doi.org/10.1002/adma.201705328 \(2018\).\r:77)/F 4/H/N/Rect[224.431 291.77 227.281 281.59]/Subtype/Link/Type/Annot>> endobj 26 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:7. Large, D. E., Abdelmessih, R. G., Fink, E. A. & Auguste, D. T. Liposome composi\ tion in drug delivery design, synthesis, characterization, and clinical application. Adv. Drug Deliv. Rev. 176, 113851 \(202\ 1\).\r:78)/F 4/H/N/Rect[250.33 227.27 252.697 217.09]/Subtype/Link/Type/Annot>> endobj 27 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:10. Jeong, H.-H., Choi, E., Ellis, E. & Lee, T.-C. Recent advances in gold nanopar\ ticles for biomedical applications: from hybrid structures to multi-functionality. J. Mater. Chem. B 7, 3480 3496 \(2019\).\r\ :79)/F 4/H/N/Rect[255.603 227.27 260.92 217.09]/Subtype/Link/Type/Annot>> endobj 28 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:11. Paunovska, K. et al. A direct comparison of in vitro and in vivo nucleic acid \ delivery mediated by hundreds of nanoparticles reveals a weak correlation. Nano Lett. 18, 2148 2157 \(2018\).\r:80)/F 4/H/N/Rect[96.3694 162.77 100.627 152.59]/Subtype/Link/Type/Annot>> endobj 29 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:12. Pardi, N. et al. Expression kinetics of nucleoside-modified mRNA delivered in \ lipid nanoparticles to mice by various routes. J. Control. Rel. 217, 345 351 \(2015\).\r:81)/F 4/H/N/Rect[107.975 130.52 112.953 120.34]/Subtype/Link/Type/Annot>> endobj 30 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:Box 1\rMechanisms of nanoparticle targeting\rMultiple mechanisms can be utilized sepa\ rately or in combination \nto control where in the body nanoparticles accumulate \(see the figure\). The final nanoparticle desig\ n will reflect how these mechanisms are :82)/F 4/H/N/Rect[122.578 119.77 125.918 109.59]/Subtype/Link/Type/Annot>> endobj 31 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/XObject<>>> endobj 32 0 obj <>stream x]rqo'H\uǩGv~RMіc"Ɨ#e_7|0؝o`F&O%gw͗ߞ7_GQpxs &ypr B6HM0J s8?u:[U崎Uiҟs=ќ?&QD8Y ?Q/.~/\HCqث`}xMügz_0bk'T8_QI(c_7~FY3{T2;0U׎mC}ƙ z V1]6b&y1U]&:8[lzгpI;'PV䳓-=zpu .mWS g>/iQphiq06v5Ck-`.X=-ո.7[Mn.9hANP w0Ss1V ͹}ꃁ] 'v\wDS`GcE77lطf?M>SN뻘xUL}&ooq8o?8/~8_a|DRs[p{>iUGIǥ\m7EMcr;݄E}$G-s:%g} LG.OϦ$^Ճ>v&1:vʀB-[)8r Q{WN*iO;4|t3hs5|Z\#IDRDxȟ>On.լd[)daų2s2o %0/(0#;:MDd^hHf*`|Zri6jOk3yIY6u}LQ|ݵ0=y암 9岡(:QJ˳ǗCP_N(w jMpo|kjTf̊P2GA'ݾS)Sc#h:!8挿Š7$ Z\ `MCGWqapa5~tuJjDLRaGelI5@9xj rfsD|sD)"9ȳŻ:K߶=)\B7i"&g?nCl6tgssA _+! 47_#y-4`KkFfx7=Vk{H|}ә ka|MI)iYf!,3x*!{V6y^iQ&MMCes?o|un=DTнYr6S2%4>m6_E H. 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Eygeris, Y., Patel, S., Jozic, A. & Sahay, G. Deconvoluting lipid nanoparticle\ structure for messenger RNA delivery. Nano Lett. 20, 4543 4549 \(2020\).\r:101)/F 4/H/N/Rect[265.643 87.5204 271.009 77.3399]/Subtype/Link/Type/Annot>> endobj 37 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:24. Samaridou, E., Heyes, J. & Lutwyche, P. Lipid nanoparticles for nucleic acid d\ elivery: current perspectives. Adv. Drug Deliv. Rev. 154 155, 37 63 \(2020\).\r:102)/F 4/H/N/Rect[370.782 76.7704 376.459 66.5899]/Subtype/Link/Type/Annot>> endobj 38 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:15. Zhang, Y., Sun, C., Wang, C., Jankovic, K. E. & Dong, Y. Lipids and lipid de\ rivatives for RNA delivery. Chem. Rev. 121, 12181 12277 \(2021\).\r:103)/F 4/H/N/Rect[332.73 55.2704 337.422 45.0899]/Subtype/Link/Type/Annot>> endobj 39 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:221. Sun, W., Hu, Q., Ji, W., Wright, G. & Gu, Z. 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Conway, A. et al. Non-viral delivery of zinc finger nuclease mRNA enables high\ ly efficient in vivo genome editing of multiple therapeutic gene targets. Mol. Ther. 27, 866 877 \(2019\).\r:104)/F 4/H/N/Rect[327.794 119.77 333.187 109.59]/Subtype/Link/Type/Annot>> endobj 329 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:27. Semple, S. C. et al. Rational design of cationic lipids for siRNA delivery. N\ at. Biotechnol. 28, 172 176 \(2010\).\r:105)/F 4/H/N/Rect[335.861 119.77 340.887 109.59]/Subtype/Link/Type/Annot>> endobj 330 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:28. Akinc, A. et al. A combinatorial library of lipid-like materials for delivery \ of RNAi therapeutics. Nat. Biotechnol. 26, 561 569 \(2008\).\r:106)/F 4/H/N/Rect[379.367 119.77 385.122 109.59]/Subtype/Link/Type/Annot>> endobj 331 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:31. Whitehead, K. A. et al. Degradable lipid nanoparticles with predictable in viv\ o siRNA delivery activity. Nat. Commun. 5, 4277 \(2014\).\r:107)/F 4/H/N/Rect[388.047 119.77 392.968 109.59]/Subtype/Link/Type/Annot>> endobj 332 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:32. Dong, Y. et al. Lipopeptide nanoparticles for potent and selective siRNA deliv\ ery in rodents and nonhuman primates. Proc. Natl Acad. Sci. USA 111, 3955 3960 \(2014\).\r:108)/F 4/H/N/Rect[446.552 119.77 452.02 109.59]/Subtype/Link/Type/Annot>> endobj 333 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:33. Fenton, O. S. et al. Bioinspired alkenyl amino alcohol ionizable lipid materia\ ls for highly potent in vivo mRNA delivery. Adv. Mater. 28, 2939 2943 \(2016\).\r:109)/F 4/H/N/Rect[453.437 119.77 458.855 109.59]/Subtype/Link/Type/Annot>> endobj 334 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:34. Zhou, K. et al. Modular degradable dendrimers enable small RNAs to extend surv\ ival in an aggressive liver cancer model. Proc. Natl Acad. Sci. USA 113, 520 525 \(2016\).\r:110)/F 4/H/N/Rect[443.044 109.02 448.796 98.8399]/Subtype/Link/Type/Annot>> endobj 335 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:36. Zhou, K. et al. Hydrophobic domain structure of linear-dendritic poly\(ethylene\ glycol\) lipids affects RNA delivery of lipid nanoparticles. Mol. Pharm. 17, 1575 1585 \(2020\).\r:111)/F 4/H/N/Rect[451.668 109.02 457.305 98.8399]/Subtype/Link/Type/Annot>> endobj 336 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:37. Liu, J. et al. Fast and efficient CRISPR/Cas9 genome editing in vivo enabled b\ y bioreducible lipid and messenger RNA nanoparticles. Adv. Mater. 31, e1902575 \n\(2019\).\r:112)/F 4/H/N/Rect[532.889 109.02 537.857 98.8399]/Subtype/Link/Type/Annot>> endobj 337 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:40. 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 \(2021\).\r:\ 113)/F 4/H/N/Rect[540.729 109.02 546.834 98.8399]/Subtype/Link/Type/Annot>> endobj 338 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:41. Li, B. et al. An orthogonal array optimization of lipid-like nanoparticles for\ mRNA delivery in vivo. Nano Lett. 15, 8099 8107 \(2015\).\r:114)/F 4/H/N/Rect[326.954 98.2704 331.857 88.0899]/Subtype/Link/Type/Annot>> endobj 339 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:42. Miller, J. B. et al. Non-viral CRISPR/Cas gene editing in vitro and in vivo en\ abled by synthetic nanoparticle co-delivery of Cas9 mRNA and sgRNA. Angew. Chem. Int. Ed. 56, 1059 1063 \(2017\).\r:115)/F 4/H/N/Rect[427.302 98.2704 432.742 88.0899]/Subtype/Link/Type/Annot>> endobj 340 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:43. Yu, X. et al. Lipid-modified aminoglycosides for mRNA delivery to the liver. \ Adv. Healthc. Mater. 9, e1901487 \(2020\).\r:116)/F 4/H/N/Rect[548.888 98.2704 554.229 88.0899]/Subtype/Link/Type/Annot>> endobj 341 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:44. Zhang, Y. et al. Lipid-modified aminoglycoside derivatives for in vivo siRNA d\ elivery. \nAdv. Mater. 25, 4641 4645 \(2013\).\r:117)/F 4/H/N/Rect[555.454 98.2704 561.26 88.0899]/Subtype/Link/Type/Annot>> endobj 342 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:45. Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-select\ ive mRNA delivery and CRISPR Cas gene editing. Nat. Mater. 20, 701 710 \(2021\).\r:118)/F 4/H/N/Rect[414.56 87.5204 419.834 77.3399]/Subtype/Link/Type/Annot>> endobj 343 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:26. Sabnis, S. et al. A novel amino lipid series for mRNA delivery: improved endos\ omal escape and sustained pharmacology and safety in non-human primates. Mol. Ther. 26, 1509 1519 \(2018\).\r:119)/F 4/H/N/Rect[373.462 55.2704 378.811 45.0899]/Subtype/Link/Type/Annot>> endobj 344 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:46. Hassett, K. J. et al. Optimization of lipid nanoparticles for intramuscular ad\ ministration of mRNA vaccines. Mol. Ther. 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Cancer nanomedicine: is targeting our target? Nat. Rev. Ma\ ter. 1, 16069 \(2016\).\r:183)/F 4/H/N/Rect[377.575 173.52 383.299 163.34]/Subtype/Link/Type/Annot>> endobj 436 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:85. Doudna, J. A. The promise and challenge of therapeutic genome editing. Natu\ re 578, 229 236 \(2020\).\r:184)/F 4/H/N/Rect[490.046 130.52 495.323 120.34]/Subtype/Link/Type/Annot>> endobj 437 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:86. Tenzer, S. et al. Rapid formation of plasma protein corona critically affects \ nanoparticle pathophysiology. Nat. 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Nanoparticle cell interactions: molecular stru\ cture of the protein corona and cellular outcomes. Acc. Chem. Res. 47, 2651 2659 \(2014\).\r:199)/F 4/H/N/Rect[230.223 195.02 235.924 184.84]/Subtype/Link/Type/Annot>> endobj 487 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:101. Li, Z. et al. Emerging well-tailored nanoparticulate delivery system based on\ in situ regulation of the protein corona. J. Control. Rel. 320, 1 18 \(2020\).\r:200)/F 4/H/N/Rect[238.68 195.02 245.779 184.84]/Subtype/Link/Type/Annot>> endobj 488 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:101. Li, Z. et al. Emerging well-tailored nanoparticulate delivery system based o\ n in situ regulation of the protein corona. J. Control. Rel. 320, 1 18 \(2020\).\r:201)/F 4/H/N/Rect[176.077 162.77 183.422 152.59]/Subtype/Link/Type/Annot>> endobj 489 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:102. Walkey, C. D. & Chan, W. C. Understanding and controlling the interaction of \ nanomaterials with proteins in a physiological environment. Chem. Soc. Rev. 41, 2780 2799 \(2012\).\r:202)/F 4/H/N/Rect[184.784 162.77 192.694 152.59]/Subtype/Link/Type/Annot>> endobj 490 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:103. Tietjen, G. T., Bracaglia, L. G., Saltzman, W. M. & Pober, J. S. Focus on fun\ damentals: achieving effective nanoparticle targeting. Trends Mol. Med. 24, 598 606 \(2018\).\r:203)/F 4/H/N/Rect[120.354 119.77 128.048 109.59]/Subtype/Link/Type/Annot>> endobj 491 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:104. Poon, W. et al. Elimination pathways of nanoparticles. ACS Nano 13, 5785 \ 5798 \(2019\).\r:204)/F 4/H/N/Rect[237.173 87.5204 245.354 77.3399]/Subtype/Link/Type/Annot>> endobj 492 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:105. Chow, A., Brown, B. D. & Merad, M. 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EMBO J. 30, 3481 3500 \(20\ 11\).\r:239)/F 4/H/N/Rect[341.609 66.0204 348.517 55.8399]/Subtype/Link/Type/Annot>> endobj 539 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:142. Smith, S. A., Selby, L. I., Johnston, A. P. R. & Such, G. K. The endosomal es\ cape of nanoparticles: toward more efficient cellular delivery. Bioconjug. 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Rel. 288, 23 33 \(2018\).\r:261)/F 4/H/N/Rect[73.1894 87.5204 80.4361 77.3399]/Subtype/Link/Type/Annot>> endobj 684 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:69. Rybakova, Y. et al. mRNA delivery for therapeutic anti-HER2 antibody expressi\ on in vivo. Mol. Ther. 27, 1415 1423 \(2019\).\r:262)/F 4/H/N/Rect[146.692 76.7704 151.877 66.5899]/Subtype/Link/Type/Annot>> endobj 685 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:70. Stadler, C. R. et al. Elimination of large tumors in mice by mRNA-encoded bis\ pecific antibodies. Nat. Med. 23, 815 817 \(2017\).\r:263)/F 4/H/N/Rect[153.197 76.7704 158.833 66.5899]/Subtype/Link/Type/Annot>> endobj 686 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:158. Kose, N. et al. A lipid-encapsulated mRNA encoding a potently neutralizing hu\ man monoclonal antibody protects against chikungunya infection. Sci. 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Ionizable amino-polyesters synthesized via ring openin\ g polymerization of tertiary amino-alcohols for tissue selective mRNA delivery. Adv. Mater. https://doi.org/10.1002/adma.201\ 801151 \(2018\).\r:303)/F 4/H/N/Rect[285.365 576.92 290.75 567.365]/Subtype/Link/Type/Annot>> endobj 885 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:186. Kusumoto, K. et al. Lipid envelope-type nanoparticle incorporating a multifun\ ctional peptide for systemic siRNA delivery to the pulmonary endothelium. ACS Nano 7, 7534 7541 \(2013\).\r:304)/F 4/H/N/Rect[277.448 554.695 283.876 545.14]/Subtype/Link/Type/Annot>> endobj 886 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:187. Hagino, Y., Khalil, I. A., Kimura, S., Kusumoto, K. & Harashima, H. GALA-modi\ fied lipid nanoparticles for the targeted delivery of plasmid DNA to the lungs. Mol. 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Highly efficient CD4+ T cell targeting and genetic recombi\ nation using engineered CD4+ cell-homing mRNA-LNPs. Mol. Ther. 29, 3293 3304 \(2021\).\r:319)/F 4/H/N/Rect[277.694 405.665 284.047 396.11]/Subtype/Link/Type/Annot>> endobj 901 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:211. Rurik Joel, G. et al. 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Con\ strained nanoparticles deliver siRNA and sgRNA to T cells in vivo without targeting ligands. \nAdv. Mater. 31, e1902251 \(201\ 9\).\r:359)/F 4/H/N/Rect[321.951 205.77 329.405 195.59]/Subtype/Link/Type/Annot>> endobj 938 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:194. Zhao, X. et al. Imidazole-based synthetic lipidoids for in vivo mRNA delivery\ into primary T lymphocytes. Angew. Chem. Int. Ed. 59, 20083 20089 \(2020\).\r:360)/F 4/H/N/Rect[474.91 205.77 482.675 195.59]/Subtype/Link/Type/Annot>> endobj 939 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:195. Ramishetti, S. et al. A combinatorial library of lipid nanoparticles for RNA \ delivery to leukocytes. Adv. Mater. 32, e1906128 \(2020\).\r:361)/F 4/H/N/Rect[479.127 195.02 486.388 184.84]/Subtype/Link/Type/Annot>> endobj 940 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:196. Kimura, S., Khalil, I. A., Elewa, Y. H. A. & Harashima, H. 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Highly efficient CD4+ T cell targeting and genetic recomb\ ination using engineered CD4+ cell-homing mRNA-LNPs. Mol. Ther. 29, 3293 3304 \(2021\).\r:388)/F 4/H/N/Rect[525.042 517.52 532.738 507.34]/Subtype/Link/Type/Annot>> endobj 972 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:211. Rurik Joel, G. et al. CAR T cells produced in vivo to treat cardiac injury.\ Science 375, 91 96 \(2022\).\r:389)/F 4/H/N/Rect[322.403 506.77 329.006 496.59]/Subtype/Link/Type/Annot>> endobj 973 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:211. Rurik Joel, G. et al. CAR T cells produced in vivo to treat cardiac injury\ . Science 375, 91 96 \(2022\).\r:390)/F 4/H/N/Rect[358.003 474.52 364.827 464.34]/Subtype/Link/Type/Annot>> endobj 974 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevMater_529.indd:212. Veiga, N. et al. Cell specific delivery of modified mRNA expressing therapeut\ ic proteins to leukocytes. Nat. 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Dilliard Daniel J. 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