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Association of Reduced Apical Untwisting With Incident HF in Asymptomatic Patients With HF Risk Factors Intravascular ultrasound guidance improves clinical outcomes during implantation of both first- and second-generation drug-eluting stents: a meta-analysis Utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention for type C lesions The effect of complete percutaneous revascularisation with and without intravascular ultrasound guidance in the drugeluting stent era Economic and Quality-of-Life Outcomes of Natriuretic Peptide–Guided Therapy for Heart Failure Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality: A Meta-analysis of Population-Based Studies INTERMACS Profiles and Outcomes Among Non–Inotrope-Dependent Outpatients With Heart Failure and Reduced Ejection Fraction A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation) Sex differences in left main coronary artery stenting: Different characteristics but similar outcomes for women compared with men Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial

Original Research2017 Aug 24;548(7668):413-419.

JOURNAL:Nature. Article Link

Correction of a pathogenic gene mutation in human embryos

Ma H, Marti-Gutierrez N, Mitalipov S et al. Keywords: genome editing; MYBPC3 mutation; inherited hypertrophic cardiomyopathy

ABSTRACT

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations.