Adams, D. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379, 11–21 (2018).
Google Scholar
Garrelfs, S. F. et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N. Engl. J. Med. 384, 1216–1226 (2021).
Google Scholar
Balwani, M. et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N. Engl. J. Med. 382, 2289–2301 (2020).
Google Scholar
Ray, K. K. et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N. Engl. J. Med. 382, 1507–1519 (2020).
Google Scholar
Finkel, R. S. et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med. 377, 1723–1732 (2017).
Google Scholar
Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2020).
Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).
Google Scholar
Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222–226 (2017).
Google Scholar
Nair, J. K. et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J. Am. Chem. Soc. 136, 16958–16961 (2014).
Google Scholar
Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).
Google Scholar
Akinc, A. et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18, 1357–1364 (2010).
Google Scholar
Willoughby, J. L. S. et al. Evaluation of GalNAc-siRNA conjugate activity in pre-clinical animal models with reduced asialoglycoprotein receptor expression. Mol. Ther. 26, 105–114 (2018).
Google Scholar
Lisowski, L. et al. Selection and evaluation of clinically relevant AAV variants in a xenograft liver model. Nature 506, 382–386 (2014).
Google Scholar
Paulk, N. K. et al. Bioengineered AAV capsids with combined high human liver transduction in vivo and unique humoral seroreactivity. Mol. Ther. 26, 289–303 (2018).
Google Scholar
Vercauteren, K. et al. Superior in vivo transduction of human hepatocytes using engineered AAV3 capsid. Mol. Ther. 24, 1042–1049 (2016).
Google Scholar
Pei, X. et al. Development of AAV variants with human hepatocyte tropism and neutralizing antibody escape capacity. Mol. Ther. Methods Clin. Dev. 18, 259–268 (2020).
Google Scholar
Wilson, E. M. et al. Extensive double humanization of both liver and hematopoiesis in FRGN mice. Stem Cell Res. 13, 404–412 (2014).
Google Scholar
Foquet, L. et al. Successful engraftment of human hepatocytes in uPA-SCID and FRG® KO mice. Methods Mol. Biol. 1506, 117–130 (2017).
Google Scholar
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).
Google Scholar
Sago, C .D. et al. Modifying a commonly expressed endocytic receptor retargets nanoparticles in vivo. Nano Lett. 18, 7590–7600 (2018).
Google Scholar
Sago, C. D. et al. Nanoparticles that deliver RNA to bone marrow identified by in vivo directed evolution. J. Am. Chem. Soc. 140, 17095–17105 (2018).
Google Scholar
Sago, C. D. et al. High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing. Proc. Natl Acad. Sci. USA 115, E9944–E9952 (2018).
Google Scholar
Tiwari, P. M. et al. Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection. Nat. Commun. 9, 3999 (2018).
Paunovska, K. et al. Nanoparticles containing oxidized cholesterol deliver mRNA to the liver microenvironment at clinically relevant doses. Adv. Mater. 31, e1807748 (2019).
Dong, Y. et al. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. Proc. Natl Acad. Sci. USA 111, 3955–3960 (2014).
Google Scholar
Dahlman, J. E. et al. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat. Nanotechnol. 9, 648–655 (2014).
Google Scholar
Lokugamage, M. P. et al. Mild innate immune activation overrides efficient nanoparticle-mediated RNA delivery. Adv. Mater. 32, 1904905 (2020).
Google Scholar
Paunovska, K. et al. Analyzing 2000 in vivo drug delivery data points reveals cholesterol structure impacts nanoparticle delivery. ACS Nano 12, 8341–8349 (2018).
Google Scholar
Patel, S. et al. Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA. Nat. Commun. 11, 983 (2020).
Google Scholar
Mui, B. L. et al. Influence of polyethylene glycol lipid desorption rates on pharmacokinetics and pharmacodynamics of siRNA lipid nanoparticles. Mol. Ther. Nucleic Acids 2, e139 (2013).
Google Scholar
Kaczmarek, J. C. et al. Optimization of a degradable polymer-lipid nanoparticle for potent systemic delivery of mRNA to the lung endothelium and immune cells. Nano Lett. 18, 6449–6454 (2018).
Google Scholar
Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396–401 (2016).
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).
Google Scholar
Lokugamage, M. P., Sago, C. D. & Dahlman, J. E. Testing thousands of nanoparticles in vivo using DNA barcodes. Curr. Opin. Biomed. Eng. 7, 1–8 (2018).
Patel, S. et al. Boosting intracellular delivery of lipid nanoparticle-encapsulated mRNA. Nano Lett. 17, 5711–5718 (2017).
Google Scholar
Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171–181 (2014).
Google Scholar
Ge, S. X., Son, E. W. & Yao, R. iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinformatics 19, 534 (2018).
Google Scholar
Low, J. Z. B., Khang, T. F. & Tammi, M. T. CORNAS: coverage-dependent RNA-Seq analysis of gene expression data without biological replicates. BMC Bioinformatics 18, 575 (2017).
Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).
Google Scholar
Szklarczyk, D. et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res. 45, D362–D368 (2017).
Google Scholar
Dobrovolskaia, M. A., Shurin, M. & Shvedova, A. A. Current understanding of interactions between nanoparticles and the immune system. Toxicol. Appl. Pharmacol. 299, 78–89 (2016).
Google Scholar
Azuma, H. et al. Robust expansion of human hepatocytes in Fah–/–/Rag2–/–/Il2rg–/– mice. Nat. Biotechnol. 25, 903–910 (2007).
Google Scholar

