RNA-silencing nanoprobes for effective activation and dynamic imaging of neural stem cell differentiation

Zhang, Ruili; Wang, Zhe; Zuo, Yi; Wang, Linlin; Wang, Zhongdi; Chen, Baihang; Wang, Zhongliang; Tian, Jie

doi:10.7150/thno.35032

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Various nanomaterials, such as inorganic nanoparticles, polymer nanoparticles, DNA nanostructures, and lipid nanoparticles, have shown great potential in stem cell therapy of neurodegenerative diseases. [72][73][74][75][76][77][78][79] Among them, composite nanocarriers, which have multiple functions and can act coordinately and synergistically with each other, have attracted increasing attention. Zhang et al constructed a traceable PCB-based poly (2-hydroxyethyl methacrylate)-RA-poly (carboxybetaine) cell-penetrating peptide (PHEMA-RA-PCB-CPP)/SPIONs/siSOX9 delivery system with temporally controlled release of siSOX9 and RA, which can effectively control the differentiation of NSCs into neurons and significantly improve the cognition and memory of AD mice.…”

Section: Nanomaterials As Carriers To Deliver Drugs and Stem Cells Fo...mentioning

confidence: 99%

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach

Wei¹,

Yang²,

Li³

2023

IJN

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Neurodegeneration is characterized by progressive, disabling, and incurable neurological disorders with the massive loss of specific neurons. As one of the most promising potential therapeutic strategies for neurodegenerative diseases, stem cell therapy exerts beneficial effects through different mechanisms, such as direct replacement of damaged or lost cells, secretion of neurotrophic and growth factors, decreased neuroinflammation, and activation of endogenous stem cells. However, poor survival and differentiation rates of transplanted stem cells, insufficient homing ability, and difficulty tracking after transplantation limit their further clinical use. The rapid development of nanotechnology provides many promising nanomaterials for biomedical applications, which already have many applications in neurodegenerative disease treatment and seem to be able to compensate for some of the deficiencies in stem cell therapy, such as transport of stem cells/genes/drugs, regulating stem cell differentiation, and real-time tracking in stem cell therapy. Therefore, nanotherapeutic strategies combined with stem cell therapy is a promising therapeutic approach to treating neurodegenerative diseases. The present review systematically summarizes recent advances in stem cell therapeutics and nanotherapeutic strategies and highlights how they can be combined to improve therapeutic efficacy for the treatment of neurodegenerative diseases.

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Section: Nanomaterials As Carriers To Deliver Drugs and Stem Cells Fo...mentioning

confidence: 99%

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach

Wei¹,

Yang²,

Li³

2023

IJN

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“…Microsatellite repeat expansions encoding toxic repetitive RNA have also been found in patients with Huntington's disease 34 . Therefore, high-performance mRNA imaging would have tremendous investigatory and diagnostic utility for neuropsychiatric diseases 35 , 36 .…”

Section: Resultsmentioning

confidence: 99%

CRISPR-Sunspot: Imaging of endogenous low-abundance RNA at the single-molecule level in live cells

Sun¹,

Chen²,

Ye³

et al. 2020

Theranostics

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CRISPR/Cas-based mRNA imaging has been developed to labeling of high-abundance mRNAs. A lack of non-genetically encoded mRNA-tagged imaging tools has limited our ability to explore the functional distributions of endogenous low-abundance mRNAs in cells. Here, we developed a CRISPR-Sunspot method based on the SunTag signal amplification system that allows efficient imaging of low-abundance mRNAs with CRISPR/Cas9. Methods: We created a stable TRE3G-dCas9-EGFP cell line and generated an Inducible dCas9-EGFP imaging system for assessment of two factors, sgRNA and dCas9, which influence imaging quality. Based on SunTag system, we established a CRISPR-Sunspot imaging system for amplifying signals from single-molecule mRNA in live cells. CRISPR-Sunspot was used to track co-localization of Camk2a mRNA with regulatory protein Xlr3b in neurons. CRISPR-Sunspot combined with CRISPRa was used to determine elevated mRNA molecules. Results: Our results showed that manipulating the expression of fluorescent proteins and sgRNA increased the efficiency of RNA imaging in cells. CRISPR-Sunspot could target endogenous mRNAs in the cytoplasm and amplified signals from single-molecule mRNA. Furthermore, CRISPR-Sunspot was also applied to visualize mRNA distributions with its regulating proteins in neurons. CRISPR-Sunspot detected the co-localization of Camk2a mRNA with overexpressed Xlr3b proteins in the neuronal dendrites. Moreover, we also manipulated CRISPR-Sunspot to detect transcriptional activation of target gene such as HBG1 in live cells. Conclusion: Our findings suggest that CRISPR-Sunspot is a novel applicable imaging tool for visualizing the distributions of low-abundance mRNAs in cells. This study provides a novel strategy to unravel the molecular mechanisms of diseases caused by aberrant mRNA molecules.

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“…The nanocomplexes were cleaved by glutathione to release SOX9 siRNA to guide neural stem cell differentiation. [ 125 ] A redox‐sensitive nanoparticle consisting of heparin sodium‐bridged disulfide bond can deliver miRNA and pDNA successfully. Such a system is potentially useful in the rehabilitation of myocardial infarction.…”

Section: Stimulus‐responsive Nanocarrier Delivery Systemsmentioning

confidence: 99%

Recent Advances in Stimulus‐Responsive Nanocarriers for Gene Therapy

Cheng

et al. 2021

Advanced Science

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Gene therapy provides a promising strategy for curing monogenetic disorders and complex diseases. However, there are challenges associated with the use of viral delivery vectors. The advent of nanomedicine represents a quantum leap in the application of gene therapy. Recent advances in stimulus-responsive nonviral nanocarriers indicate that they are efficient delivery systems for loading and unloading of therapeutic nucleic acids. Some nanocarriers are responsive to cues derived from the internal environment, such as changes in pH, redox potential, enzyme activity, reactive oxygen species, adenosine triphosphate, and hypoxia. Others are responsive to external stimulations, including temperature gradients, light irradiation, ultrasonic energy, and magnetic field. Multiple stimuli-responsive strategies have also been investigated recently for experimental gene therapy.

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RNA-silencing nanoprobes for effective activation and dynamic imaging of neural stem cell differentiation

Cited by 6 publications

References 31 publications

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach

CRISPR-Sunspot: Imaging of endogenous low-abundance RNA at the single-molecule level in live cells

Recent Advances in Stimulus‐Responsive Nanocarriers for Gene Therapy

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