CRISPR-Based Synthetic Transcription Factors In Vivo: The Future of Therapeutic Cellular Programming

Matthew Pandelakis, Elizabeth Delgado, Mo R. Ebrahimkhani

Research output: Contribution to journalReview article

Abstract

Pinpoint control over endogenous gene expression in vivo has long been a fevered dream for clinicians and researchers alike. With the recent repurposing of programmable, RNA-guided DNA endonucleases from the CRISPR bacterial immune system, this dream is becoming a powerful reality. Engineered CRISPR/Cas9-based transcriptional regulators and epigenome editors have enabled researchers to perturb endogenous gene expression in vivo, allowing for the therapeutic reprogramming of cell and tissue behavior. For this technology to be of maximal use, a variety of technological hurdles still need to be addressed. Better understanding of the design principle controlling gene expression together with technologies that enable spatiotemporal control of transcriptional engineering are fundamental for rational design, improved efficacy, and ultimately safe translation to humans. In this review, we will discuss recent advances and integrative strategies that can help pave the path toward a new class of transcriptional therapeutics. Pinpoint control over endogenous gene expression in vivo has long been a fevered dream for clinicians and researchers alike. With the recent repurposing of programmable, RNA-guided DNA endonucleases from the CRISPR bacterial immune system, this dream is becoming a powerful reality. Engineered CRISPR/Cas9-based transcriptional regulators and epigenome editors have enabled researchers to perturb endogenous gene expression in vivo, allowing for the therapeutic reprogramming of cell and tissue behavior. For this technology to be of maximal use, a variety of technological hurdles still need to be addressed. Better understanding of the design principle controlling gene expression together with technologies that enable spatiotemporal control of transcriptional engineering are fundamental for rational design, improved efficacy, and ultimately safe translation to humans. In this review, we will discuss recent advances and integrative strategies that can help pave the path toward a new class of transcriptional therapeutics.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalCell Systems
Volume10
Issue number1
DOIs
StatePublished - Jan 22 2020
Externally publishedYes

Keywords

  • Cas9
  • CRISPR
  • epigenome editing
  • in vivo cellular programing
  • synthetic gene circuits
  • synthetic transcription factor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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