Simultaneous high-efficiency base editing and reprogramming of patient fibroblasts

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu


Human induced pluripotent stem cells (hiPSCs) allow in vitro study of genetic diseases and hold potential for personalized stem cell therapy. Gene editing, precisely modifying specifically targeted loci, represents a valuable tool for different hiPSC applications. This is especially useful in monogenic diseases to dissect the function of unknown mutations or to create genetically corrected, patient-derived hiPSCs. Here we describe a highly efficient method for simultaneous base editing and reprogramming of fibroblasts employing a CRISPR-Cas9 adenine base editor. As a proof of concept, we apply this approach to generate gene-edited hiPSCs from skin biopsies of four patients carrying a Finnish-founder pathogenic point mutation in either NOTCH3 or LDLR genes. We also show LDLR activity restoration after the gene correction. Overall, this method yields tens of gene-edited hiPSC monoclonal lines with unprecedented efficiency and robustness while considerably reducing the cell culture time and thus the risk for in vitro alterations.
LehtiStem cell reports
DOI - pysyväislinkit
TilaJulkaistu - 24 marrask. 2021
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu


  • 1184 Genetiikka, kehitysbiologia, fysiologia
  • 1182 Biokemia, solu- ja molekyylibiologia
  • 318 Lääketieteen bioteknologia

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