Efficient Precision Genome Editing in iPSCs via Genetic Co-targeting with Selection

نویسندگان

  • Katie A. Mitzelfelt
  • Chris McDermott-Roe
  • Michael N. Grzybowski
  • Maribel Marquez
  • Chieh-Ti Kuo
  • Michael Riedel
  • Shuping Lai
  • Melinda J. Choi
  • Kurt D. Kolander
  • Daniel Helbling
  • David P. Dimmock
  • Michele A. Battle
  • Chuanchau J. Jou
  • Martin Tristani-Firouzi
  • James W. Verbsky
  • Ivor J. Benjamin
  • Aron M. Geurts
چکیده

Genome editing in induced pluripotent stem cells is currently hampered by the laborious and expensive nature of identifying homology-directed repair (HDR)-modified cells. We present an approach where isolation of cells bearing a selectable, HDR-mediated editing event at one locus enriches for HDR-mediated edits at additional loci. This strategy, called co-targeting with selection, improves the probability of isolating cells bearing HDR-mediated variants and accelerates the production of disease models.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Genome editing in human stem cells.

The use of custom-engineered sequence-specific nucleases (including CRISPR/Cas9, ZFN, and TALEN) allows genetic changes in human cells to be easily made with much greater efficiency and precision than before. Engineered double-stranded DNA breaks can efficiently disrupt genes, or, with the right donor vector, engineer point mutations and gene insertions. However, a number of design consideratio...

متن کامل

Induced pluripotent stem cells (iPSCs) based approaches for hematopoietic cancer therapy

Induced pluripotent stem cells (iPSCs) are reprogrammed from somatic cells through numerous transcription factors. Human induced pluripotent stem cell approaches are developing as a hopeful strategy to improve our knowledge of genetic association studies and the underlying molecular mechanisms.  Rapid progression in stem cell therapy and cell reprogramming provides compelling reasons for its fe...

متن کامل

Precision genome editing in plants via gene targeting and piggyBac-mediated marker excision

Precise genome engineering via homologous recombination (HR)-mediated gene targeting (GT) has become an essential tool in molecular breeding as well as in basic plant science. As HR-mediated GT is an extremely rare event, positive-negative selection has been used extensively in flowering plants to isolate cells in which GT has occurred. In order to utilize GT as a methodology for precision muta...

متن کامل

CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and reversal of chemosensitivity in human epithelial ovarian cancer cell line

Objective(s): Multidrug resistance (MDR) is a major obstacle in the successful chemotherapy of ovarian cancer. Inhibition of P-glycoprotein (P-gp), a member of ATP-binding cassette (ABC) transporters, is a well-known strategy to overcome MDR in cancer. The aim of this study was to investigate the efficiency and ability of CRISPR/Cas9 genome editing technology to knockdown ABCB1 gene expression ...

متن کامل

Stem Cells Application in Modeling of Human Genetic Diseases

The use of animal models in modeling of human genetic disease has many advantages. In some cases, however, this method may not be applicable due to some limitations, such as differences in tissue composition, anatomy and physiology of humans and animals. Isogenic human disease models are a population of cells that are selected or engineered to model a specific genetic disease, in vitro. They ar...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017