TY - JOUR
T1 - CRISPR-Based Synthetic Transcription Factors In Vivo
T2 - The Future of Therapeutic Cellular Programming
AU - Pandelakis, Matthew
AU - Delgado, Elizabeth
AU - Ebrahimkhani, Mo R.
N1 - Funding Information:
The authors wish to thank Dr. Samira Kiani for comments and critical discussions during the preparation of the manuscript. M.R.E. is supported by R01 EB02456 from NIH-NIBIB , R01HL141805 from NIH-NHLBI , and Arizona Biomedical Research Council New Investigator Award ( ADHS16-162402 ).
Funding Information:
The authors wish to thank Dr. Samira Kiani for comments and critical discussions during the preparation of the manuscript. M.R.E. is supported by R01 EB02456 from NIH-NIBIB, R01HL141805 from NIH-NHLBI, and Arizona Biomedical Research Council New Investigator Award (ADHS16-162402). M.P. and M.R.E. discussed the topics, developed the ideas, and wrote the majority of the manuscript. E.D. contributed to the writing of the manuscript. E.D. and M.R.E. generated the figures.
Publisher Copyright:
© 2019 The Authors
PY - 2020/1/22
Y1 - 2020/1/22
N2 - 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.
AB - 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.
KW - CRISPR
KW - Cas9
KW - epigenome editing
KW - in vivo cellular programing
KW - synthetic gene circuits
KW - synthetic transcription factor
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U2 - 10.1016/j.cels.2019.10.003
DO - 10.1016/j.cels.2019.10.003
M3 - Review article
C2 - 31972154
AN - SCOPUS:85077776067
SN - 2405-4712
VL - 10
SP - 1
EP - 14
JO - Cell Systems
JF - Cell Systems
IS - 1
ER -