Redox-Responsive Phase-Separating Peptide as a Universal Delivery Vehicle for CRISPR/Cas9 Genome Editing Machinery

Yue Sun, Xiaojie Xu, Liwei Chen, Wei Leong Chew, Yuan Ping, Ali Miserez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

CRISPR/Cas9-based genome editing tools have enormous potential for the development of various therapeutic treatments due to their reliability and broad applicability. A central requirement of CRISPR/Cas9 is the efficient intracellular delivery of the editing machinery, which remains a well-recognized challenge, notably to deliver Cas9 in its native protein form. Herein, a phase-separating peptide with intracellular redox-triggered release properties is employed to encapsulate and deliver all three forms of CRISRP-Cas9 editing machinery, namely, pDNA, mRNA/sgRNA, and the ribonucleoprotein complex. These modalities are readily recruited within peptide coacervates during liquid-liquid phase separation by simple mixing and exhibit higher transfection and editing efficiency compared to highly optimized commercially available transfection reagents currently used for genome editing.

Original languageEnglish
Pages (from-to)16597-16606
Number of pages10
JournalACS Nano
Volume17
Issue number17
DOIs
Publication statusPublished - Sept 12 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

ASJC Scopus Subject Areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy

Keywords

  • CRISPR/Cas9
  • drug delivery
  • genome editing
  • liquid−liquid phase separation
  • peptides

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