Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities

Yueh Chien; Yu Jer Hsiao; Shih Jie Chou; Ting Yi Lin; Aliaksandr A. Yarmishyn; Wei Yi Lai; Meng Shiue Lee; Yi Ying Lin; Tzu Wei Lin; De Kuang Hwang; Tai Chi Lin; Shih Hwa Chiou; Shih Jen Chen; Yi Ping Yang

doi:10.1186/s12951-022-01717-x

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities

Yueh Chien, Yu Jer Hsiao, Shih Jie Chou, Ting Yi Lin, Aliaksandr A. Yarmishyn, Wei Yi Lai, Meng Shiue Lee, Yi Ying Lin, Tzu Wei Lin, De Kuang Hwang, Tai Chi Lin, Shih Hwa Chiou^*, Shih Jen Chen, Yi Ping Yang^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

19 Scopus citations

Abstract

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Original language	English
Article number	511
Journal	Journal of Nanobiotechnology
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12951-022-01717-x
State	Published - Dec 2022

Keywords

CRISPR-Cas9
Inherited retinal disease
Nanoparticle
Patient-derived iPSCs
Retinal organoid

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12951-022-01717-x

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Chien, Y., Hsiao, Y. J., Chou, S. J., Lin, T. Y., Yarmishyn, A. A., Lai, W. Y., Lee, M. S., Lin, Y. Y., Lin, T. W., Hwang, D. K., Lin, T. C., Chiou, S. H., Chen, S. J., & Yang, Y. P. (2022). Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities. Journal of Nanobiotechnology, 20(1), Article 511. https://doi.org/10.1186/s12951-022-01717-x

@article{2d725397b91d4c7993767aa983adb3aa,

title = "Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities",

abstract = "Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.",

keywords = "CRISPR-Cas9, Inherited retinal disease, Nanoparticle, Patient-derived iPSCs, Retinal organoid",

author = "Yueh Chien and Hsiao, {Yu Jer} and Chou, {Shih Jie} and Lin, {Ting Yi} and Yarmishyn, {Aliaksandr A.} and Lai, {Wei Yi} and Lee, {Meng Shiue} and Lin, {Yi Ying} and Lin, {Tzu Wei} and Hwang, {De Kuang} and Lin, {Tai Chi} and Chiou, {Shih Hwa} and Chen, {Shih Jen} and Yang, {Yi Ping}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s12951-022-01717-x",

language = "English",

volume = "20",

journal = "Journal of Nanobiotechnology",

issn = "1477-3155",

publisher = "BioMed Central",

number = "1",

}

Chien, Y, Hsiao, YJ, Chou, SJ, Lin, TY, Yarmishyn, AA, Lai, WY, Lee, MS, Lin, YY, Lin, TW, Hwang, DK, Lin, TC, Chiou, SH, Chen, SJ & Yang, YP 2022, 'Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities', Journal of Nanobiotechnology, vol. 20, no. 1, 511. https://doi.org/10.1186/s12951-022-01717-x

TY - JOUR

T1 - Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases

T2 - applications, challenges, and emerging opportunities

AU - Chien, Yueh

AU - Hsiao, Yu Jer

AU - Chou, Shih Jie

AU - Lin, Ting Yi

AU - Yarmishyn, Aliaksandr A.

AU - Lai, Wei Yi

AU - Lee, Meng Shiue

AU - Lin, Yi Ying

AU - Lin, Tzu Wei

AU - Hwang, De Kuang

AU - Lin, Tai Chi

AU - Chiou, Shih Hwa

AU - Chen, Shih Jen

AU - Yang, Yi Ping

PY - 2022/12

Y1 - 2022/12

N2 - Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

AB - Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

KW - CRISPR-Cas9

KW - Inherited retinal disease

KW - Nanoparticle

KW - Patient-derived iPSCs

KW - Retinal organoid

UR - http://www.scopus.com/inward/record.url?scp=85143148358&partnerID=8YFLogxK

U2 - 10.1186/s12951-022-01717-x

DO - 10.1186/s12951-022-01717-x

M3 - Review article

C2 - 36463195

AN - SCOPUS:85143148358

SN - 1477-3155

VL - 20

JO - Journal of Nanobiotechnology

JF - Journal of Nanobiotechnology

IS - 1

M1 - 511

ER -

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities

Abstract

Keywords

UN SDGs

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