CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations

The CRISPR-Cas9 technology, one of the groundbreaking genome editing methods for addressing genetic disorders, has emerged as a powerful, precise, and efficient tool. However, its clinical translation remains hindered by challenges in delivery efficiency and targeting specificity. This review provid...

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Main Authors: Hyunwoo Lee, Won-Yeop Rho, Yoon-Hee Kim, Hyejin Chang, Bong-Hyun Jun
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/3/542
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author Hyunwoo Lee
Won-Yeop Rho
Yoon-Hee Kim
Hyejin Chang
Bong-Hyun Jun
author_facet Hyunwoo Lee
Won-Yeop Rho
Yoon-Hee Kim
Hyejin Chang
Bong-Hyun Jun
author_sort Hyunwoo Lee
collection DOAJ
description The CRISPR-Cas9 technology, one of the groundbreaking genome editing methods for addressing genetic disorders, has emerged as a powerful, precise, and efficient tool. However, its clinical translation remains hindered by challenges in delivery efficiency and targeting specificity. This review provides a comprehensive analysis of the structural features, advantages, and potential applications of various non-viral and stimuli-responsive systems, examining recent progress to emphasize the potential to address these limitations and advance CRISPR-Cas9 therapeutics. We describe how recent reports emphasize that nonviral vectors, including lipid-based nanoparticles, extracellular vesicles, polymeric nanoparticles, gold nanoparticles, and mesoporous silica nanoparticles, can offer diverse advantages to enhance stability, cellular uptake, and biocompatibility, based on their structures and physio-chemical stability. We also summarize recent progress on stimuli-responsive nanoformulations, a type of non-viral vector, to introduce precision and control in CRISPR-Cas9 delivery. Stimuli-responsive nanoformulations are designed to respond to pH, redox states, and external triggers, facilitate controlled and targeted delivery, and minimize off-target effects. The insights in our review suggest future challenges for clinical applications of gene therapy technologies and highlight the potential of delivery systems to enhance CRISPR-Cas9’s clinical efficacy, positioning them as pivotal tools for future gene-editing therapies.
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spelling doaj-art-b8981b775fad422fa35b088d90aa2c0a2025-08-20T02:48:07ZengMDPI AGMolecules1420-30492025-01-0130354210.3390/molecules30030542CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive NanoformulationsHyunwoo Lee0Won-Yeop Rho1Yoon-Hee Kim2Hyejin Chang3Bong-Hyun Jun4Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of KoreaSchool of International Engineering and Science, Jeonbuk National University, Jeonju 54896, Republic of KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of KoreaDivision of Science Education, Kangwon National University, 1 Gangwondaehakgil, Chuncheon-si 24341, Republic of KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of KoreaThe CRISPR-Cas9 technology, one of the groundbreaking genome editing methods for addressing genetic disorders, has emerged as a powerful, precise, and efficient tool. However, its clinical translation remains hindered by challenges in delivery efficiency and targeting specificity. This review provides a comprehensive analysis of the structural features, advantages, and potential applications of various non-viral and stimuli-responsive systems, examining recent progress to emphasize the potential to address these limitations and advance CRISPR-Cas9 therapeutics. We describe how recent reports emphasize that nonviral vectors, including lipid-based nanoparticles, extracellular vesicles, polymeric nanoparticles, gold nanoparticles, and mesoporous silica nanoparticles, can offer diverse advantages to enhance stability, cellular uptake, and biocompatibility, based on their structures and physio-chemical stability. We also summarize recent progress on stimuli-responsive nanoformulations, a type of non-viral vector, to introduce precision and control in CRISPR-Cas9 delivery. Stimuli-responsive nanoformulations are designed to respond to pH, redox states, and external triggers, facilitate controlled and targeted delivery, and minimize off-target effects. The insights in our review suggest future challenges for clinical applications of gene therapy technologies and highlight the potential of delivery systems to enhance CRISPR-Cas9’s clinical efficacy, positioning them as pivotal tools for future gene-editing therapies.https://www.mdpi.com/1420-3049/30/3/542CRISPR-Cas9gene therapynon-viral delivery systemsstimuli-responsivestimuli-responsive nanomaterials
spellingShingle Hyunwoo Lee
Won-Yeop Rho
Yoon-Hee Kim
Hyejin Chang
Bong-Hyun Jun
CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations
Molecules
CRISPR-Cas9
gene therapy
non-viral delivery systems
stimuli-responsive
stimuli-responsive nanomaterials
title CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations
title_full CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations
title_fullStr CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations
title_full_unstemmed CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations
title_short CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations
title_sort crispr cas9 gene therapy non viral delivery and stimuli responsive nanoformulations
topic CRISPR-Cas9
gene therapy
non-viral delivery systems
stimuli-responsive
stimuli-responsive nanomaterials
url https://www.mdpi.com/1420-3049/30/3/542
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AT wonyeoprho crisprcas9genetherapynonviraldeliveryandstimuliresponsivenanoformulations
AT yoonheekim crisprcas9genetherapynonviraldeliveryandstimuliresponsivenanoformulations
AT hyejinchang crisprcas9genetherapynonviraldeliveryandstimuliresponsivenanoformulations
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