Hu, P. et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease. Circulation 1411742–1759 (2020).
Google Scholar
Nordestgaard, B. G. et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur. Heart J. 343478–3490 (2013).
Google Scholar
Ference, B. A. et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 382459–2472 (2017).
Google Scholar
Abifadel, M. et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34154–156 (2003).
Google Scholar
Watts, G. F. et al. International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia. Nat. Rev. Cardiol. 20845–869 (2023).
Google Scholar
Zhao, S. P., Yu, B. L., Peng, D. Q. & Huo, Y. The effect of moderate-dose versus double-dose statins on patients with acute coronary syndrome in China: results of the CHILLAS trial. Atherosclerosis 233707–712 (2014).
Google Scholar
Li, J. J. et al. 2023 Chinese guideline for lipid management. Front. Pharmacol. 141190934 (2023).
Google Scholar
Cainzos-Achirica, M., Martin, S. S., Cornell, J. E., Mulrow, C. D. & Guallar, E. PCSK9 inhibitors: a new era in lipid-lowering treatment?. Ann. Intern. With. 16364–65 (2015).
Google Scholar
Seidah , NG , Awan , Z. , Chrétien , M. & Mbikay , M. PCSK9: a key modulator of cardiovascular health . Circ. Res. 1141022–1036 (2014).
Google Scholar
Kastelein, J. J. et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur. Heart J. 362996–3003 (2015).
Google Scholar
Raal, F. J. et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 385331–340 (2015).
Google Scholar
Raal, F. J. et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N. Engl. J. Med. 3821520–1530 (2020).
Google Scholar
Langslet, G. et al. Thirty percent of children and young adults with familial hypercholesterolemia treated with statins have adherence issues. Am. J. Prev. Cardiol. 6100180 (2021).
Google Scholar
Wu, Y. et al. Highly efficient therapeutic gene editing of human hematopoietic stem cells. Night. With. 25776–783 (2019).
Google Scholar
Fu, B. et al. CRISPR–Cas9-mediated gene editing of the BCL11A enhancer for pediatric β0/β0 transfusion-dependent β-thalassemia. Night. With. 281573–1580 (2022).
Google Scholar
Zeng, J. et al. Therapeutic base editing of human hematopoietic stem cells. Night. With. 26535–541 (2020).
Google Scholar
Frangoul, H. et al. CRISPR–Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 384252–260 (2021).
Google Scholar
Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385493–502 (2021).
Google Scholar
Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337816–821 (2012).
Google Scholar
Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339819–823 (2013).
Google Scholar
Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339823–826 (2013).
Google Scholar
Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551464–471 (2017).
Google Scholar
Richter, M. F. et al. Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat. Biotechnol. 38883–891 (2020).
Google Scholar
Liao, J. et al. Sequential amino acid mutagenesis-driven de novo evolution of adenine deaminases enables efficient in vivo base editing in primate. Preprint at bioRxiv https://doi.org/10.1101/2025.05.14.653640 (2025).
Kasiewicz, L. N. et al. GalNAc-lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy. Nat. Common. 142776 (2023).
Google Scholar
Grünewald, J. et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569433–437 (2019).
Google Scholar
Cuchel, M. et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur. Heart J. 352146–2157 (2014).
Google Scholar
Hermel, M. et al. Highlights of cardiovascular disease prevention studies presented at the 2023 American Heart Association Scientific Sessions. Curr. Atheroscler. Rep. 26119–131 (2024).
Google Scholar
Gurevitz, C. et al. Gene therapy and genome editing for lipoprotein disorders. Eur. Heart J. 463420–3433 (2025).
Google Scholar
Vafai, S. et al. Abstract 4139206: Design of Heart-2: a phase 1b clinical trial of VERVE-102, an in vivo base editing medicine delivered by a GalNAc-LNP and targeting PCSK9 to durably lower LDL cholesterol. Circulation 150A4139206 (2024).
Google Scholar
Ndeupen, S. et al. The mRNA-LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience 24103479 (2021).
Google Scholar
Feng, Y. et al. Albumin-recruiting lipid nanoparticle potentiates the safety and efficacy of mRNA vaccines by avoiding liver accumulation. Night. Mater. 241826–1839 (2025).
Kawaguchi, Y. et al. Modulating immunogenicity and reactogenicity in mRNA-lipid nanoparticle vaccines through lipid component optimization. ACS Nano 1927977–28001 (2025).
Google Scholar
Davies, N. et al. Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein. Mol. Ther. Nucleic Acids 24369–384 (2021).
Google Scholar
Maeder, M. L. et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Night. With. 25229–233 (2019).
Google Scholar
Chavez, M., Chen, X., Finn, P. B. & Qi, L. S. Advances in CRISPR therapeutics. Nat. Rev. Nephrol. 199–22 (2023).
Google Scholar
Akinc, A. et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 181357–1364 (2010).
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. 13616958–16961 (2014).
Google Scholar
Li, J. J. et al. Chinese expert consensus on the clinical diagnosis and management of statin intolerance. Clin. Pharmacol. Ther. 115954–964 (2024).
Google Scholar
Finn, J. D. et al. A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 222227–2235 (2018).
