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Designing Biomimicking Synthetic Transcription Factors for Therapeutic Gene Modulation

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Cell-Inspired Materials and Engineering

Part of the book series: Fundamental Biomedical Technologies ((FBMT))

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Abstract

Inside living cells, natural transcription factors operate by precisely recognizing specific DNA sequences and by recruiting transcription ON/OFF epigenetic marks at a precise locus and time. Hence, designing synthetic transcription factors that mimic the programmable functionality of the biological transcription factors is complicated because of the need to integrate multiple functions onto a single molecular platform. Large-scale sequencing studies have been providing an enormous wealth of information about the critical DNA sequences and the transcription factors that coordinate the intricate transcription machinery in the natural cellular environment. Using this collected biological information, programmable DNA-binding natural proteins and small molecules have been developed to mimic and/or modulate transcription factors in a sequence-specific manner. Small-molecule transcription factor mimics operate to regulate gene expression inside living cells in a transgene-free and cost-effective manner. Hairpin pyrrole–imidazole polyamides (PIPs) are selective DNA-binding small molecules that can be preprogrammed to read specific DNA sequences. PIPs and their conjugates have been developed to mimic transcription factors regarding structure and function and generate epigenetic codes for gene regulation. In this chapter, we detail the progress of small-molecule-based transcription factor mimics and their prospects in therapeutic gene modulation.

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Authors and Affiliations

  1. Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan

    Ganesh N. Pandian

  2. Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan

    Hiroshi Sugiyama

Authors
  1. Ganesh N. Pandian
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  2. Hiroshi Sugiyama
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Correspondence to Ganesh N. Pandian or Hiroshi Sugiyama .

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  1. Kyoto University iCeMS, Sakyo-ku, Kyoto, Japan

    Dan Ohtan Wang

  2. Kyoto University iCeMS, Sakyo-ku, Kyoto, Japan

    Daniel Packwood

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Pandian, G.N., Sugiyama, H. (2021). Designing Biomimicking Synthetic Transcription Factors for Therapeutic Gene Modulation. In: Wang, D.O., Packwood, D. (eds) Cell-Inspired Materials and Engineering. Fundamental Biomedical Technologies. Springer, Cham. https://doi.org/10.1007/978-3-030-55924-3_6

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