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).
Adams, D. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379, 11–21 (2018).
Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).
Verve Therapeutics doses first human with an investigational in vivo base editing medicine, VERVE-101, as a potential treatment for heterozygous familial hypercholesterolemia. Verve Therapeutics https://ir.vervetx.com/news-releases/news-release-details/verve-therapeutics-doses-first-human-investigational-vivo-base (2022).
Longhurst, H. J. et al. CRISPR–Cas9 in vivo gene editing of KLKB1 for hereditary angioedema. N. Engl. J. Med. 390, 432–441 (2024).
Ferrari, G., Thrasher, A. J. & Aiuti, A. Gene therapy using haematopoietic stem and progenitor cells. Nat. Rev. Genet. 22, 216–234 (2021).
Salinas Cisneros, G. & Thein, S. L. Recent advances in the treatment of sickle cell disease. Front. Physiol. 11, 435 (2020).
Taher, A. T., Musallam, K. M. & Cappellini, M. D. β-thalassemias. N. Engl. J. Med. 384, 727–743 (2021).
Cazzola, M. Introduction to a review series on inherited anemias. Blood 136, 1215–1216 (2020).
Castagnoli, R., Delmonte, O. M., Calzoni, E. & Notarangelo, L. D. Hematopoietic stem cell transplantation in primary immunodeficiency diseases: current status and future perspectives. Front. Pediatr. 7, 295 (2019).
Tan, E. Y., Boelens, J. J., Jones, S. A. & Wynn, R. F. Hematopoietic stem cell transplantation in inborn errors of metabolism. Front. Pediatr. 7, 433 (2019).
Eichler, F. et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N. Engl. J. Med. 377, 1630–1638 (2017).
Frangoul, H. et al. CRISPR–Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 384, 252–260 (2021).
Locatelli, F. et al. Betibeglogene autotemcel gene therapy for non-β0/β0 genotype β-thalassemia. N. Engl. J. Med. 386, 415–427 (2021).
Kanter, J. et al. Biologic and clinical efficacy of LentiGlobin for sickle cell disease. N. Engl. J. Med. 386, 617–628 (2022).
Domingues, M. J., Nilsson, S. K. & Cao, B. New agents in HSC mobilization. Int. J. Hematol. 105, 141–152 (2017).
Atilla, E., Ataca Atilla, P. & Demirer, T. A review of myeloablative vs reduced intensity/non-myeloablative regimens in allogeneic hematopoietic stem cell transplantations. Balkan Med. J. 34, 1–9 (2017).
Shi, D., Toyonaga, S. & Anderson, D. G. In vivo RNA delivery to hematopoietic stem and progenitor cells via targeted lipid nanoparticles. Nano Lett. 23, 2938–2944 (2023).
Breda, L. et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science 381, 436–443 (2023).
Breda, L. et al. In vivo modification of hematopoietic stem cells by targeted lipid nanoparticles encapsulating mRNA. Blood 140, 305–306 (2022).
Li, C. et al. Safe and efficient in vivo hematopoietic stem cell transduction in nonhuman primates using HDAd5/35++ vectors. Mol. Ther. Methods Clin. Dev. 24, 127–141 (2022).
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).
Eygeris, Y., Patel, S., Jozic, A. & Sahay, G. Deconvoluting lipid nanoparticle structure for messenger RNA delivery. Nano Lett. 20, 4543–4549 (2020).
Kulkarni, J. A., Witzigmann, D., Leung, J., Tam, Y. Y. C. & Cullis, P. R. On the role of helper lipids in lipid nanoparticle formulations of siRNA. Nanoscale 11, 21733–21739 (2019).
Kauffman, K. J. et al. Rapid, single-cell analysis and discovery of vectored mRNA transfection in vivo with a loxP-flanked tdTomato reporter mouse. Mol. Ther. Nucleic Acids 10, 55–63 (2018).
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).
LoPresti, S. T., Arral, M. L., Chaudhary, N. & Whitehead, K. A. The replacement of helper lipids with charged alternatives in lipid nanoparticles facilities targeted mRNA delivery to the spleen and lungs. J. Control. Release 345, 819–831 (2022).
Radmand, A. et al. The transcriptional response to lung-targeting lipid nanoparticles in vivo. Nano Lett. 23, 993–1002 (2023).
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).
Dobrowolski, C. et al. Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery. Nat. Nanotechnol. 17, 871–879 (2022).
Tiwari, P. M. et al. Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection. Nat. Commun. 9, 3999 (2018).
Hatit, M. Z. C. et al. Species-dependent in vivo mRNA delivery and cellular responses to nanoparticles. Nat. Nanotechnol. 17, 310–318 (2022).
Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2019).
Jurecic, R. Hematopoietic stem cell heterogeneity. Adv. Exp. Med. Biol. 1169, 195–211 (2019).
Kim, J., Eygeris, Y., Ryals, R. C., Jozić, A. & Sahay, G. Strategies for non-viral vectors targeting organs beyond the liver. Nat. Nanotechnol. 19, 428–447 (2023).
Finn, J. D. et al. A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 22, 2227–2235 (2018).
Kiel, M. J. et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121, 1109–1121 (2005).
Le, T. et al. BBrowser: making single-cell data easily accessible. Preprint at bioRxiv https://doi.org/10.1101/2020.12.11.414136 (2020).
Moreno, A. et al. Anti-PEG antibodies inhibit the anticoagulant activity of PEGylated aptamers. Cell Chem. Biol. 26, 634–644 (2019).
Urits, I. et al. A review of patisiran (ONPATTRO®) for the treatment of polyneuropathy in people with hereditary transthyretin amyloidosis. Neurol. Ther. 9, 301–315 (2020).
FDA cellular & gene therapy guidances. US Food and Drug Administration https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances (2022).
Tarantal, A. F., Noctor, S. C. & Hartigan-O’Connor, D. J. Nonhuman primates in translational research. Annu. Rev. Anim. Biosci. 10, 441–468 (2022).
Lindsay, K. E. et al. Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV. Mol. Ther. 28, 805–819 (2020).
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).
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).
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
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).
Dahlman, J. E. et al. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat. Nanotechnol. 9, 648–655 (2014).
Sager, H. B. et al. RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Sci. Transl. Med. 8, 342ra80 (2016).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
McGinnis, C. S., Murrow, L. M. & Gartner, Z. J. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 8, 329–337(2019).
Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865–868 (2017).
Ni, H. et al. Piperazine-derived lipid nanoparticles deliver mRNA to immune cells in vivo. Nat. Commun. 13, 4766 (2022).
Tarantal, A. F. in Handbook of Experimental Animals, The Laboratory Primate (ed. Wolfe-Coote, S.) 317–352 (Elsevier Academic Press, 2005).
Tarantal, A. F. et al. Nonmyeloablative conditioning regimen to increase engraftment of gene-modified hematopoietic stem cells in young rhesus monkeys. Mol. Ther. 20, 1033–1045 (2012).
Guo, C., Liu, W., Hua, X., Li, H. & Jia, S. Fourier light-field microscopy. Opt. Express 27, 25573–25594 (2019).
Hua, X., Liu, W. & Jia, S. High-resolution Fourier light-field microscopy for volumetric multi-color live-cell imaging. Optica 8, 614–620 (2021).
Sternberg, S. Biomedical image processing. Computer 16, 22–34 (1983).
Mandracchia, B. et al. Fast and accurate sCMOS noise correction for fluorescence microscopy. Nat. Commun. 11, 94 (2020).
Saha, K. et al. The NIH somatic cell genome editing program. Nature 592, 195–204 (2021).
