Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct

Seongchan Kim; You Kyeong Jeong; Chang Sik Cho; Seok Hoon Lee; Chang Ho Sohn; Jeong Hun Kim; Youngdo Jeong; Dong Hyun Jo; Sangsu Bae; Hyojin Lee

doi:10.1002/adhm.202201825

Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct

Seongchan Kim, You Kyeong Jeong, Chang Sik Cho, Seok Hoon Lee, Chang Ho Sohn, Jeong Hun Kim, Youngdo Jeong, Dong Hyun Jo, Sangsu Bae, Hyojin Lee

Yonsei Advanced Science Institute

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

1 Citation (Scopus)

Abstract

Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.

Original language	English
Article number	2201825
Journal	Advanced Healthcare Materials
Volume	12
Issue number	4
DOIs	https://doi.org/10.1002/adhm.202201825
Publication status	Published - 2023 Feb 6

Bibliographical note

Funding Information:
S.K. and Y.K.J. contributed equally to this work. This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2020M3A9I4038197 to Y.J. and H.L., 2020M3A9I4036072 to S.B., 2022R1C1C2007247 to S.K., and 2022R1A2C1003768 to D.H.J.), the Ministry of Education (Grant No. 2020R1A6A3A01098476 to S.K.), and the KIST project (Grant No. 2E31641 to H.L.). The authors thank Seung Hoe Kim and Kyungwoo Lee at KIST for experimental assistance and graphic design of Figures; Dr. Hong Yeol Yoon at KIST for technical support regarding in vivo mouse whole‐body imaging; Dong‐Jun Koo at Seoul National University for 3D rendering of volume images; and Prof. Jae‐Sung Woo at Korea University for providing highly purified ABE and CBE proteins (AncBE4max and ABEmax).

Funding Information:
S.K. and Y.K.J. contributed equally to this work. This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2020M3A9I4038197 to Y.J. and H.L., 2020M3A9I4036072 to S.B., 2022R1C1C2007247 to S.K., and 2022R1A2C1003768 to D.H.J.), the Ministry of Education (Grant No. 2020R1A6A3A01098476 to S.K.), and the KIST project (Grant No. 2E31641 to H.L.). The authors thank Seung Hoe Kim and Kyungwoo Lee at KIST for experimental assistance and graphic design of Figures; Dr. Hong Yeol Yoon at KIST for technical support regarding in vivo mouse whole-body imaging; Dong-Jun Koo at Seoul National University for 3D rendering of volume images; and Prof. Jae-Sung Woo at Korea University for providing highly purified ABE and CBE proteins (AncBE4max and ABEmax).

Publisher Copyright:
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

All Science Journal Classification (ASJC) codes

Biomaterials
Biomedical Engineering
Pharmaceutical Science

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10.1002/adhm.202201825

Cite this

@article{ecc061a3e6c94af3b0dbce778d00d279,

title = "Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct",

abstract = "Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.",

author = "Seongchan Kim and Jeong, {You Kyeong} and Cho, {Chang Sik} and Lee, {Seok Hoon} and Sohn, {Chang Ho} and Kim, {Jeong Hun} and Youngdo Jeong and Jo, {Dong Hyun} and Sangsu Bae and Hyojin Lee",

note = "Funding Information: S.K. and Y.K.J. contributed equally to this work. This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2020M3A9I4038197 to Y.J. and H.L., 2020M3A9I4036072 to S.B., 2022R1C1C2007247 to S.K., and 2022R1A2C1003768 to D.H.J.), the Ministry of Education (Grant No. 2020R1A6A3A01098476 to S.K.), and the KIST project (Grant No. 2E31641 to H.L.). The authors thank Seung Hoe Kim and Kyungwoo Lee at KIST for experimental assistance and graphic design of Figures; Dr. Hong Yeol Yoon at KIST for technical support regarding in vivo mouse whole‐body imaging; Dong‐Jun Koo at Seoul National University for 3D rendering of volume images; and Prof. Jae‐Sung Woo at Korea University for providing highly purified ABE and CBE proteins (AncBE4max and ABEmax). Funding Information: S.K. and Y.K.J. contributed equally to this work. This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2020M3A9I4038197 to Y.J. and H.L., 2020M3A9I4036072 to S.B., 2022R1C1C2007247 to S.K., and 2022R1A2C1003768 to D.H.J.), the Ministry of Education (Grant No. 2020R1A6A3A01098476 to S.K.), and the KIST project (Grant No. 2E31641 to H.L.). The authors thank Seung Hoe Kim and Kyungwoo Lee at KIST for experimental assistance and graphic design of Figures; Dr. Hong Yeol Yoon at KIST for technical support regarding in vivo mouse whole-body imaging; Dong-Jun Koo at Seoul National University for 3D rendering of volume images; and Prof. Jae-Sung Woo at Korea University for providing highly purified ABE and CBE proteins (AncBE4max and ABEmax). Publisher Copyright: {\textcopyright} 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.",

year = "2023",

month = feb,

day = "6",

doi = "10.1002/adhm.202201825",

language = "English",

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T1 - Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct

AU - Kim, Seongchan

AU - Jeong, You Kyeong

AU - Cho, Chang Sik

AU - Lee, Seok Hoon

AU - Sohn, Chang Ho

AU - Kim, Jeong Hun

AU - Jeong, Youngdo

AU - Jo, Dong Hyun

AU - Bae, Sangsu

AU - Lee, Hyojin

N1 - Funding Information: S.K. and Y.K.J. contributed equally to this work. This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2020M3A9I4038197 to Y.J. and H.L., 2020M3A9I4036072 to S.B., 2022R1C1C2007247 to S.K., and 2022R1A2C1003768 to D.H.J.), the Ministry of Education (Grant No. 2020R1A6A3A01098476 to S.K.), and the KIST project (Grant No. 2E31641 to H.L.). The authors thank Seung Hoe Kim and Kyungwoo Lee at KIST for experimental assistance and graphic design of Figures; Dr. Hong Yeol Yoon at KIST for technical support regarding in vivo mouse whole‐body imaging; Dong‐Jun Koo at Seoul National University for 3D rendering of volume images; and Prof. Jae‐Sung Woo at Korea University for providing highly purified ABE and CBE proteins (AncBE4max and ABEmax). Funding Information: S.K. and Y.K.J. contributed equally to this work. This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2020M3A9I4038197 to Y.J. and H.L., 2020M3A9I4036072 to S.B., 2022R1C1C2007247 to S.K., and 2022R1A2C1003768 to D.H.J.), the Ministry of Education (Grant No. 2020R1A6A3A01098476 to S.K.), and the KIST project (Grant No. 2E31641 to H.L.). The authors thank Seung Hoe Kim and Kyungwoo Lee at KIST for experimental assistance and graphic design of Figures; Dr. Hong Yeol Yoon at KIST for technical support regarding in vivo mouse whole-body imaging; Dong-Jun Koo at Seoul National University for 3D rendering of volume images; and Prof. Jae-Sung Woo at Korea University for providing highly purified ABE and CBE proteins (AncBE4max and ABEmax). Publisher Copyright: © 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

PY - 2023/2/6

Y1 - 2023/2/6

N2 - Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.

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Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct

Abstract

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