Engineered zinc finger DNA-binding domains: Synthesis, assessment of DNA-binding affinity, and direct protein delivery to mammalian cells

Mir A. Hossain, Isaac J. Knudson, Shaleen Thakur, Yong Shen, Jared R. Stees, Joeva J. Barrow, Jörg Bungert*

*Corresponding author for this work

Research output: Chapter in Book or Report/Conference proceedingChapterpeer-review

3 Citations (Scopus)

Abstract

Zinc finger proteins are the most common among families of DNA-binding transcription factors. Designer transcription factors generated by the fusion of engineered zinc finger DNA-binding domains (ZF-DBDs) to effector domains have been valuable tools for the modulation of gene expression and for targeted genome editing. However, ZF-DBDs without effector domains have also been shown to effectively modulate gene expression by competing with sequence-specific DNA-binding transcription factors. Here, we describe the methodology and provide a detailed workflow for the cloning, expression, purification, and direct cell delivery of engineered ZF-DBDs. Using this protocol, ZF-DBDs can be generated with high efficiency in less than 2 weeks. We also describe a nonradioactive method for measuring DNA binding affinity of the purified ZF-DBD proteins as well as a method for direct delivery of the purified ZF-DBDs to mammalian cells.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages361-375
Number of pages15
DOIs
Publication statusPublished - 2017
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1654
ISSN (Print)1064-3745

Keywords

  • Direct protein delivery
  • Electrophoretic mobility shift assay
  • Engineered zinc finger DNA-binding domain
  • Modular assembly
  • Recombinant protein purification

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