Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs

Ning Sun, Huimin Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Sickle cell disease (SCD) is the most common human genetic disease which is caused by a single mutation of human β-globin (HBB) gene. The lack of long-term treatment makes the development of reliable cell and gene therapies highly desirable. Disease-specific patient-derived human induced pluripotent stem cells (hiPSCs) have great potential for developing novel cell and gene therapies. With the disease-causing mutations corrected in situ, patient-derived hiPSCs can restore normal cell functions and serve as a renewable autologous cell source for the treatment of genetic disorders. Here we successfully utilized transcription activator-like effector nucleases (TALENs), a recently emerged novel genome editing tool, to correct the SCD mutation in patient-derived hiPSCs. The TALENs we have engineered are highly specific and generate minimal off-target effects. In combination with piggyBac transposon, TALEN-mediated gene targeting leaves no residual ectopic sequences at the site of correction and the corrected hiPSCs retain full pluripotency and a normal karyotype. Our study demonstrates an important first step of using TALENs for the treatment of genetic diseases such as SCD, which represents a significant advance toward hiPSC-based cell and gene therapies. Biotechnol. Biotechnol. Bioeng. 2014;111: 1048-1053.

Original languageEnglish (US)
Pages (from-to)1048-1053
Number of pages6
JournalBiotechnology and bioengineering
Volume111
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Gene therapy
  • Genome editing
  • Induced pluripotent stem cells
  • piggyBac transposon
  • Sickle cell disease
  • TAL effector nucleases

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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