Magnetogenetics with Piezo1 Mechanosensitive Ion Channel for CRISPR Gene Editing

Wookjin Shin; Sumin Jeong; Jung Uk Lee; Soo Yeun Jeong; Jeonghong Shin; Hyongbum Henry Kim; Jinwoo Cheon; Jae Hyun Lee

doi:10.1021/acs.nanolett.2c02314

Magnetogenetics with Piezo1 Mechanosensitive Ion Channel for CRISPR Gene Editing

Wookjin Shin, Sumin Jeong, Jung Uk Lee, Soo Yeun Jeong, Jeonghong Shin, Hyongbum Henry Kim, Jinwoo Cheon, Jae Hyun Lee

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca²⁺signaling pathway, inducing the pre-encoded genes to express genes of interest (GOIs), which is Cas9 protein for the CRISPR regulation of the target proteins. We demonstrated that this magnetogenetic CRISPR system successfully edits the target genome for both in vitro and pseudo-in vivo environments, providing a versatile magnetic platform for remote gene editing of animals with various size scales.

Original language	English
Pages (from-to)	7415-7422
Number of pages	8
Journal	Nano letters
Volume	22
Issue number	18
DOIs	https://doi.org/10.1021/acs.nanolett.2c02314
Publication status	Published - 2022 Sept 28

Bibliographical note

Funding Information:
CRE-SRE-NFAT with furin-modified human insulin containing plasmid was kindly gifted by Dr. Jeffrey M. Friedman (Rockefeller University, New York, NY, USA). CRISPR reporter plasmid and sgRNA- EGFR for the CRISPR reporter assay were kind gifts from Dr. Junho K. Hur (Kyung Hee University, Seoul, Korea). We thank Dr. Minsuk Kwak for help with and discussions of this research. This work was supported by the Institute for Basic Science (IBS-R026-D1). J.-H.L. is supported by the National Research Foundation of Korea (No. 2021R1A2C1093319).

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

All Science Journal Classification (ASJC) codes

Bioengineering
Chemistry(all)
Materials Science(all)
Condensed Matter Physics
Mechanical Engineering

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10.1021/acs.nanolett.2c02314

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title = "Magnetogenetics with Piezo1 Mechanosensitive Ion Channel for CRISPR Gene Editing",

abstract = "Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca2+signaling pathway, inducing the pre-encoded genes to express genes of interest (GOIs), which is Cas9 protein for the CRISPR regulation of the target proteins. We demonstrated that this magnetogenetic CRISPR system successfully edits the target genome for both in vitro and pseudo-in vivo environments, providing a versatile magnetic platform for remote gene editing of animals with various size scales.",

author = "Wookjin Shin and Sumin Jeong and Lee, {Jung Uk} and Jeong, {Soo Yeun} and Jeonghong Shin and Kim, {Hyongbum Henry} and Jinwoo Cheon and Lee, {Jae Hyun}",

note = "Funding Information: CRE-SRE-NFAT with furin-modified human insulin containing plasmid was kindly gifted by Dr. Jeffrey M. Friedman (Rockefeller University, New York, NY, USA). CRISPR reporter plasmid and sgRNA- EGFR for the CRISPR reporter assay were kind gifts from Dr. Junho K. Hur (Kyung Hee University, Seoul, Korea). We thank Dr. Minsuk Kwak for help with and discussions of this research. This work was supported by the Institute for Basic Science (IBS-R026-D1). J.-H.L. is supported by the National Research Foundation of Korea (No. 2021R1A2C1093319). Publisher Copyright: {\textcopyright} 2022 American Chemical Society. All rights reserved.",

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AU - Cheon, Jinwoo

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N2 - Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca2+signaling pathway, inducing the pre-encoded genes to express genes of interest (GOIs), which is Cas9 protein for the CRISPR regulation of the target proteins. We demonstrated that this magnetogenetic CRISPR system successfully edits the target genome for both in vitro and pseudo-in vivo environments, providing a versatile magnetic platform for remote gene editing of animals with various size scales.

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Magnetogenetics with Piezo1 Mechanosensitive Ion Channel for CRISPR Gene Editing

Abstract

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