Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery

Xu Wang, Shuai Liu, Yehui Sun, Xueliang Yu, Sang M. Lee, Qiang Cheng, Tuo Wei, Junyu Gong, Joshua Robinson, Di Zhang, Xizhen Lian, Pratima Basak, Daniel J. Siegwart

Published: 2022-10-30 DOI: 10.1038/s41596-022-00755-x

Selective Organ Targeting

Lipid Nanoparticles

mRNA Delivery

Nucleic Acid Therapeutics

Scalable Synthesis

AI 解读

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A new methodology termed selective organ targeting (SORT) was recently developed that enables controllable delivery of nucleic acids to target tissues. SORT lipid nanoparticles (LNPs) involve the inclusion of SORT molecules that accurately tune delivery t
Introduction
Materials
Procedure
Troubleshooting
Timing
Anticipated results
References
ACKNOWLEDGMENTS
ACKNOWLEDGMENTS

Sahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics—developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014).
Hajj, K. A. & Whitehead, K. A. Tools for translation: non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2, 17056 (2017).
Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).
Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2020).
Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078–1094 (2021).
Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol. Ther. 27, 710–728 (2019).
Li, B., Zhang, X. & Dong, Y. Nanoscale platforms for messenger RNA delivery. Wiley Interdiscip. Rev. Nanomed. Nanobiotech. 11, e1530 (2019).
Wei, T. et al. Delivery of tissue-targeted scalpels: opportunities and challenges for in vivo CRISPR/Cas-based genome editing. ACS Nano 14, 9243–9262 (2020).
Kulkarni, J. A. et al. The current landscape of nucleic acid therapeutics. Nat. Nanotechnol. 16, 630–643 (2021).
Allen, T. M. & Cullis, P. R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 65, 36–48 (2013).
Alameh, M.-G. et al. Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 54, 2877–2892 (2021).
Elia, U. et al. Design of SARS-CoV-2 hFc-conjugated receptor-binding domain mRNA vaccine delivered via lipid nanoparticles. ACS Nano 15, 9627–9637 (2021).
Hassett, K. J. et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol. Ther. Nucleic Acids 15, 1–11 (2019).
McKay, P. F. et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat. Commun. 11, 3523 (2020).
Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines—a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018).
VanBlargan, L. A. et al. An mRNA vaccine protects mice against multiple tick-transmitted flavivirus infections. Cell Rep. 25, 3382–3392.e3383 (2018).
Li, B. et al. An orthogonal array optimization of lipid-like nanoparticles for mRNA delivery in vivo. Nano Lett. 15, 8099–8107 (2015).
Robinson, E. et al. Lipid nanoparticle-delivered chemically modified mRNA restores chloride secretion in cystic fibrosis. Mol. Ther. 26, 2034–2046 (2018).
Veiga, N. et al. Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes. Nat. Commun. 9, 4493 (2018).
Cheng, Q. et al. Dendrimer-based lipid nanoparticles deliver therapeutic FAH mRNA to normalize liver function and extend survival in a mouse model of hepatorenal tyrosinemia type I. Adv. Mater. 30, 1805308 (2018).
Patel, S. et al. Lipid nanoparticles for delivery of messenger RNA to the back of the eye. J. Control. Release 303, 91–100 (2019).
Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).
Han Jeong, P. et al. In vivo delivery of CRISPR–Cas9 using lipid nanoparticles enables antithrombin gene editing for sustainable hemophilia A and B therapy. Sci. Adv. 8, eabj6901 (2022).
Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR–Cas gene editing. Nat. Mater. 20, 701–710 (2021).
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).
Wei, T. et al. Systemic nanoparticle delivery of CRISPR–Cas9 ribonucleoproteins for effective tissue specific genome editing. Nat. Commun. 11, 3232 (2020).
Billingsley, M. M. et al. Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett. 20, 1578–1589 (2020).
Lee, K. et al. Adjuvant incorporated lipid nanoparticles for enhanced mRNA-mediated cancer immunotherapy. Biomater. Sci. 8, 1101–1105 (2020).
Miao, L. et al. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019).
Oberli, M. A. et al. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 17, 1326–1335 (2017).
Sahin, U. et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 585, 107–112 (2020).
Zhang, H. et al. Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling. Proc. Natl Acad. Sci. USA 118, e2005191118 (2021).
Li, W. & Szoka, F. C. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res. 24, 438–449 (2007).
Cheng, X. & Lee, R. J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev. 99, 129–137 (2016).
Jokerst, J. V., Lobovkina, T., Zare, R. N. & Gambhir, S. S. Nanoparticle PEGylation for imaging and therapy. Nanomedicine 6, 715–728 (2011).
Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).
Lee, S. M. et al. A systematic study of unsaturation in lipid nanoparticles leads to improved mRNA transfection in vivo. Angew. Chem. Int. Ed. 60, 5848–5853 (2021).
Álvarez-Benedicto, E. et al. Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA). Biomater. Sci. 10, 549–559 (2022).
Farbiak, L. et al. All-in-one dendrimer-based lipid nanoparticles enable precise HDR-mediated gene editing in vivo. Adv. Mater. 33, 2006619 (2021).
Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021).
Zhou, K. et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model. Proc. Natl Acad. Sci. USA 201520756 (2016).
Stroock Abraham, D. et al. Chaotic mixer for microchannels. Science 295, 647–651 (2002).
Chen, D. et al. Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J. Am. Chem. Soc. 134, 6948–6951 (2012).
Belliveau, N. M. et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol. Ther. Nucleic Acids 1, e37 (2012).
Swingle, K. L. et al. Amniotic fluid stabilized lipid nanoparticles for in utero intra-amniotic mRNA delivery. J. Control. Release 341, 616–633 (2022).
Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20, 101–124 (2021).
Hirai, Y. et al. Charge-reversible lipid derivative: a novel type of pH-responsive lipid for nanoparticle-mediated siRNA delivery. Int. J. Pharm. 585, 119479 (2020).
Maeta, M. et al. Vitamin E scaffolds of pH-responsive lipid nanoparticles as DNA vaccines in cancer and protozoan infection. Mol. Pharm. 17, 1237–1247 (2020).
Evers, M. J. W. et al. State-of-the-art design and rapid-mixing production techniques of lipid nanoparticles for nucleic acid delivery. Small Methods 2, 1700375 (2018).
Meure, L. A., Foster, N. R. & Dehghani, F. Conventional and dense gas techniques for the production of liposomes: a review. AAPS PharmSciTech 9, 798 (2008).
Leung, A. K. K. et al. Microfluidic mixing: a general method for encapsulating macromolecules in lipid nanoparticle systems. J. Phys. Chem. B 119, 8698–8706 (2015).
Shepherd, S. J., Issadore, D. & Mitchell, M. J. Microfluidic formulation of nanoparticles for biomedical applications. Biomaterials 274, 120826 (2021).
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).

Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery

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