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Tumor microenvironment based stimuli-responsive CRISPR/Cas delivery systems: A viable platform for interventional
Nanyang Tang1, Qian Ning2, Zewei Wang1
1Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang 421001, China; Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China.
Abstract:
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems have emerged as robust tools in cancer gene therapy due to their simplicity and versatility. Nevertheless, the genome editing efficiency in tumor sites and the clinical applications of CRISPR/Cas have been compromised by non-specific delivery and genotoxicity. Recently, intelligent delivery systems incorporating sensitive materials in response to endogenous stimuli of the tumor microenvironment (TME) have represented viable platforms for tumor-specific genome editing and reduced side effects of CRISPR/Cas. Spurred by this promising direction, this review first introduces the CRISPR/Cas systems widely employed in cancer therapeutic explorations. Various types of CRISPR/Cas delivery systems sensitive to the stimuli in TME and typical dual-/multiple-responsive CRISPR/Cas carriers are further discussed, emphasizing the correlations between sensitive components and spatiotemporal delivery mechanisms. The genome editing efficiencies of CRISPR/Cas-loaded stimuli-responsive carriers are also summarized both in vitro and in vivo. Collectively, stimuli-responsive CRISPR/Cas delivery systems hold great promise for potent cancer gene therapy.
Insights
Stimuli-responsive delivery systems enhance clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) gene therapy for cancer. These systems improve tumor-specific editing and reduce genotoxicity for better therapeutic outcomes.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Oncology
Background:
- Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems offer versatile cancer gene therapy potential.
- Challenges include non-specific delivery and genotoxicity, limiting clinical applications.
- The tumor microenvironment (TME) presents opportunities for targeted delivery strategies.
Purpose of the Study:
- To review CRISPR/Cas systems used in cancer therapy.
- To discuss stimuli-responsive delivery systems for TME-specific CRISPR/Cas applications.
- To summarize the efficiency of these advanced delivery systems.
Main Methods:
- Review of current literature on CRISPR/Cas systems in cancer gene therapy.
- Analysis of various stimuli-responsive materials and their integration into CRISPR/Cas carriers.
- Evaluation of in vitro and in vivo studies on CRISPR/Cas-loaded carriers.
Main Results:
- CRISPR/Cas systems are adaptable tools for cancer gene therapy.
- Stimuli-responsive delivery systems enable tumor-specific genome editing.
- Dual- and multiple-responsive carriers demonstrate enhanced spatiotemporal control.
- CRISPR/Cas-loaded carriers show promising editing efficiencies in preclinical models.
Conclusions:
- Stimuli-responsive CRISPR/Cas delivery systems are a promising strategy for cancer gene therapy.
- These systems can overcome limitations of non-specific delivery and genotoxicity.
- Further development holds potential for improved cancer treatment outcomes.
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