Synthetic molecular sensors based on CRISPR‐Cas9 redirect anticancer signal flows to treat retinoblastomas

Xiao, Lulu; Jun, Li; Sheng, Yiyu; Wang, Ye; Dou, Xiaoyan

doi:10.1002/ctm2.618

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…1 B). Next, the mRNA transcribed by the gene of interest was redesigned using the aptazyme (aptazyme-sensor) of theophylline referred to previous work [ 18 ] (Fig. 1 C).…”

Section: Resultsmentioning

confidence: 99%

CRISPR-based gene expression platform for precise regulation of bladder cancer

Zhan,

Li,

Liu

et al. 2024

Cell Mol Biol Lett

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The development of compact CRISPR systems has facilitated delivery but has concurrently reduced gene editing efficiency, thereby limiting the further utilization of CRISPR systems. Enhancing the efficiency of CRISPR systems poses a challenging task and holds significant implications for the advancement of biotechnology. In our work, we report a synthetic dual-antibody system that can stably exist in the intracellular environment, specifically inhibiting the functions of NF-κB and β-catenin. This not only elevates the transgenic expression of the CRISPR system by suppressing the innate immune response within cells to enhance the gene editing efficiency but also demonstrates a notable tumor inhibitory effect. Based on the specific output expression regulation of CRISPR-CasΦ, we constructed a CRISPR-based gene expression platform, which includes sensor modules for detecting intracellular β-catenin and NF-κB, as well as an SDA module to enhance overall efficiency. In vitro experiments revealed that the CRISPR-based gene expression platform exhibited superior CDK5 expression inhibition efficiency and specific cytotoxicity towards tumor cells. In vitro experiments, we found that CRISPR-based gene expression platforms can selectively kill bladder cancer cells through T cell-mediated cytotoxicity. Our design holds significant assistant potential of transgene therapy and may offer the capability to treat other diseases requiring transgene therapy.

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“…1 B). Next, the mRNA transcribed by the gene of interest was redesigned using the aptazyme (aptazyme-sensor) of theophylline referred to previous work [ 18 ] (Fig. 1 C).…”

Section: Resultsmentioning

confidence: 99%

CRISPR-based gene expression platform for precise regulation of bladder cancer

Zhan,

Li,

Liu

et al. 2024

Cell Mol Biol Lett

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“…In our study, CCK-8 assay was used to determine the cell proliferation of BCa cells. The specific steps of the experimental operation mainly refer to the instructions of manufacturer (TransGen, Beijing, China) and previous literature [19]. In short, transfected cells were inoculated in 96-well plates and their absorbance was measured at 0h, 12h, 24h, and 36h.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

Exosome-mediated delivery of artificial circular RNAs for gene therapy of bladder cancer

Zhou,

Fang,

Tang

et al. 2024

J. Cancer

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Bladder cancer (BCa) is one of the most common malignancies affecting men. Oncogenic transcription factors function as an important regulator in the progression of human cancer. In our study, we aimed to construct artificial circular non-coding RNAs (acircRNAs) consisting of three functional units that mimic the CRISPR-Cas system and elucidate its therapeutic role in bladder cancer. Additionally, the compare of the efficiency in regulating gene expression between acircRNA and CRISPR-dCas systems was performed. We connected the cDNA sequences of TFs aptamer and constructed a circRNA. To demonstrate the platform's practicality, β-catenin and NF-κB were chosen as functional targets, while T24 and 5637 cell lines served as test models. Real-time Quantitative PCR (qPCR), double luciferase assay and related phenotype assay were used to detect the expression of related genes and the therapeutic effect. To elucidate the functionality of acircRNAs, luciferase vectors capable of detecting β-catenin and NF-κB expression were employed to assess the inhibitory impact of acircRNA on β-catenin and NF-κB. Consequently, the optimal combination involving acircRNA-3 was determined. Next, qPCR assay was employed to assess the relative expression levels of target downstream genes following acircRNA treatment. The expression of c-myc and cyclin D1 were used to determine the function of β-catenin, while Bcl-XL and TRAF1 were used to determine that of NF-κB. The acircRNAs inhibited the β-catenin and NF-κB related signaling in BCa cells specifically. CD63-HuR fusion protein was used to loading acircRNA into exosomes. The results showed that acircRNA could inhibit the activity of the target transcription factors, and the inhibitory effect was better than that of CRIPSR-dCas9-KRAB. Furthermore, functional experiments demonstrated that the transfection of acircRNA in bladder cells resulted in decreased proliferation, enhanced apoptosis, and suppressed migration. In conclusion, our synthetic gene device exhibited anti-tumor regulatory capabilities and showed greater efficiency in tumor suppression compared to the CRISPR-dCas9-KRAB system. Therefore, our device provides a new strategy for cancer treatment and could be a useful strategy for cancer cells.

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“…In addition to the aforementioned treatment options, recent advancements in research have demonstrated strategies to improve therapeutic outcomes and reduce associated complications. One such promising approach involves the utilization of CRISPR Cas9 gene editing technology, which enables the precise redirection of anticancer signals to target retinoblastoma cells while preserving healthy tissue [ 61 ]. This innovative technique has great potential to enhance cancer treatment efficacy by minimizing off-target effects.…”

Section: Clinical Applications and Outcomesmentioning

confidence: 99%

Genetic Risk Factors and Clinical Outcomes in Childhood Eye Cancers: A Review

Hameed,

Yu,

Almadani

et al. 2024

Genes

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Childhood eye cancers, although rare, present substantial health challenges, affecting the pediatric population with a remarkable impact on their lives and families. This comprehensive review provides insights into the various types of ocular tumors, primarily focusing on malignant eye tumors, their genetic predispositions, and advancements in managing these conditions. Understanding the genetic risk factors is crucial for early detection, risk assessment, and the development of targeted therapies. This review discusses genome-wide association (GWAS) and next-generation sequencing (NGS) studies to find common and rare genetic variants. Furthermore, it also explores the outcomes and implications of these genetic discoveries in treating pediatric ocular cancer. These findings underscore the significance of genetic research in guiding early interventions and improving outcomes in children with ocular cancers.

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Synthetic molecular sensors based on CRISPR‐Cas9 redirect anticancer signal flows to treat retinoblastomas

Cited by 4 publications

References 9 publications

CRISPR-based gene expression platform for precise regulation of bladder cancer

CRISPR-based gene expression platform for precise regulation of bladder cancer

Exosome-mediated delivery of artificial circular RNAs for gene therapy of bladder cancer

Genetic Risk Factors and Clinical Outcomes in Childhood Eye Cancers: A Review

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