CBS 2019
CBSMD教育中心
中 文

Other Relevant Articles

Abstract

Recommended Article

Implantable Hemodynamic Monitoring for Heart Failure Patients Hs-cTroponins for the prediction of recurrent cardiovascular events in patients with established CHD - A comparative analysis from the KAROLA study Basic Biology of Oxidative Stress and the Cardiovascular System: Part 1 of a 3-Part Series Clinical Efficacy and Safety of Evolocumab in High-Risk Patients Receiving a Statin: Secondary Analysis of Patients With Low LDL Cholesterol Levels and in Those Already Receiving a Maximal-Potency Statin in a Randomized Clinical Trial Impact of Coronary Lesion Complexity in Percutaneous Coronary Intervention: One-Year Outcomes From the Large, Multicentre e-Ultimaster Registry Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction Interleukin-1 Beta as a Target for Atherosclerosis Therapy: Biological Basis of CANTOS and Beyond Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity

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.