Recent Updates of the CRISPR/Cas9 Genome Editing System: Novel Approaches to Regulate Its Spatiotemporal Control by Genetic and Physicochemical Strategies DOI Creative Commons
Khaled S. Allemailem, Ahmad Almatroudi, Arshad Husain Rahmani

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 5335 - 5363

Published: June 1, 2024

Abstract: The genome editing approach by clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) is a revolutionary advancement in genetic engineering. Owing to its simple design and powerful genome-editing capability, it offers promising strategy for the treatment of different infectious, metabolic, diseases. crystal structure Streptococcus pyogenes Cas9 (SpCas9) complex with sgRNA target DNA at 2.5 Å resolution reveals groove accommodating sgRNA:DNA heteroduplex within bilobate architecture recognition (REC) nuclease (NUC) domains. presence PAM significantly required recognition, R-loop formation, strand scission. Recently, spatiotemporal control CRISPR/Cas9 has been considerably improved genetic, chemical, physical regulatory strategies. use modifiers anti-CRISPR proteins, cell-specific promoters, histone acetyl transferases uplifted application as future-generation tool. In addition, interventions chemical control, small-molecule activators, oligonucleotide conjugates bioresponsive delivery carriers have other areas biological fields. Furthermore, intermediation using heat-, light-, magnetism-, ultrasound-responsive elements attached this molecular tool revolutionized further. These strategies reduce CRISPR/Cas9's undesirable off-target effects. However, effects still offer some challenges comprehensive clinical translation approach. review, we summarize recent advances structure, mechanistic action, role inhibitors, approaches. Finally, measurement approaches, challenges, future prospects, applications are discussed. Keywords: CRISPR/Cas9, sgRNA, editing, effects,

Language: Английский

CRISPR–Cas9 applications in T cells and adoptive T cell therapies DOI Creative Commons
Xiaoying Chen,

Shuhan Zhong,

Yonghao Zhan

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: April 12, 2024

Abstract T cell immunity is central to contemporary cancer and autoimmune therapies, encompassing immune checkpoint blockade adoptive therapies. Their diverse characteristics can be reprogrammed by different challenges dependent on antigen stimulation levels, metabolic conditions, the degree of inflammation. cell-based therapeutic strategies are gaining widespread adoption in oncology treating inflammatory conditions. Emerging researches reveal that clustered regularly interspaced palindromic repeats–associated protein 9 (CRISPR–Cas9) genome editing has enabled cells more adaptable specific microenvironments, opening door advanced therapies preclinical clinical trials. CRISPR–Cas9 edit both primary engineered cells, including CAR-T TCR-T, vivo vitro regulate differentiation activation states. This review first provides a comprehensive summary role its applications studies for We also explore application CRISPR screen high-throughput technology anticipate current limitations CRISPR–Cas9, off-target effects delivery challenges, envisioned improvements related technologies disease screening, diagnosis, treatment.

Language: Английский

Citations

16
Advanced Delivery Systems for Gene Editing: A Comprehensive Review from the GenE-HumDi COST Action Working group DOI Creative Commons
Alessia Cavazza, Francisco J Molina-Estévez, Álvaro Plaza Reyes

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102457 - 102457

Published: Jan. 18, 2025

Language: Английский

Citations

2
CRISPR/Cas detection with nanodevices: moving deeper into liquid biopsy DOI
Huimin Kong, Ke Yi, Rachel L. Mintz

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(17), P. 2301 - 2319

Published: Jan. 1, 2024

This feature article summarises the latest advances, potential challenges, and future prospects of CRISPR/Cas gene-editing technologies in conjunction with emerging nanodevices for refinement precision liquid biopsy techniques.

Language: Английский

Citations

9
A Serum Resistant Polymer with Exceptional Endosomal Escape and mRNA Delivery Efficacy for CRISPR Gene Therapy DOI Creative Commons

Jia Lv,

Qianqian Fan,

Yirou Zhang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Nanoparticle-based mRNA delivery offers a versatile platform for innovative therapies. However, most of the current systems are limited by poor serum tolerance, suboptimal endosomal escape and efficacy. Herein, highly efficient mRNA-delivering material is identified from library fluoropolymers. The lead FD17 shows exceptional stability escape, enabling into various cell types, surpassing commercial reagents such as Lipofectamine 3000. formed nanoparticles adsorb abundant albumin on surface, which facilitates cellular uptake via scavenger receptor-mediated endocytosis. enables mRNAs encoding CRE, Cas9, base editor hyCBE genome editing. mediates CRISPR/Cas9 gene therapy intraocular injection effectively down-regulates vascular endothelial growth factor A in retinal pigment epithelial cells mice, yielding promising therapeutic responses against laser-induced choroidal neovascularization. discovered this study great promise development therapeutics to combat wide range diseases.

Language: Английский

Citations

1
Behavioral Abnormalities, Cognitive Impairments, Synaptic Deficits, and Gene Replacement Therapy in a CRISPR Engineered Rat Model of 5p15.2 Deletion Associated With Cri du Chat Syndrome DOI Creative Commons
Jingjing Shen, Yan Wang, Yang Liu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract The Cri du Chat Syndrome (CdCS), a devastating genetic disorder caused by deletion on chromosome 5p, faces challenges in finding effective treatments and accurate animal models. Using CRISPR‐Cas9, novel CdCS rat model with 2q22 is developed, mirroring common alteration patients. This exhibits pronounced deficits social behavior, cognition, anxiety, accompanied neuronal abnormalities immune dysregulation key brain regions such as the hippocampus medial prefrontal cortex (mPFC). immunostaining RNA‐seq analyses provide new insights into pathogenesis, revealing inflammatory processes. Importantly, it demonstrated that early gene replacement therapy AAV‐ Ctnnd2 alleviates cognitive impairments rats, highlighting potential for intervention. However, effectiveness of this confined to developmental stages does not fully restore all symptoms. findings deepen understanding pathogenesis suggest promising therapeutic directions.

Language: Английский

Citations

1
Polymeric Nanoparticles Simultaneously Delivering Paclitaxel Prodrug and Combretastatin A4 with Exceptionally High Drug Loading for Cancer Combination Therapy DOI

Huicong Zhou,

Zhaofan Yang,

Guan-Yu Jin

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Nanomedicines capable of delivering multiple drugs have become essential in combination therapy. However, the challenges low drug loading capacity (DLC) and difficulties administering dosages between different significantly limit antitumor efficacy. In this study, a nanomedicine constructed through rational prodrug nanocarrier design was reported for cancer Initially, phenylborate ester (PBE) group-modified paclitaxel (PTX) (PTX-PBE) synthesized could self-assemble water. Subsequently, combretastatin A4 (CA4) polymer conjugates, mPEG-PCA4 (PCA4), were as nanocarriers to facilitate exceptionally high PTX-PBE precisely controlled manner. Both vitro vivo experiments demonstrated that PCA4 nanoparticles (PCA4/PTX-PBE NPs) exhibited potent efficacy favorable biocompatibility. Our approach provides straightforward, efficient, controllable strategy co-delivery pharmaceuticals clinical

Language: Английский

Citations

1
Effective Delivery of CRISPR/dCas9-SAM for Multiplex Gene Activation Based on Mesoporous Silica Nanoparticles for Bladder Cancer Therapy DOI Creative Commons

Jinming Xu,

Jiaju Xu,

Chengfang Sun

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Exploring Advanced CRISPR Delivery Technologies for Therapeutic Genome Editing DOI Creative Commons
Neda Rostami, Mohammad Mahmoudi Gomari,

Edris Choupani

et al.

Small Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 25, 2024

The genetic material within cells plays a pivotal role in shaping the structure and function of living organisms. Manipulating an organism's genome to correct inherited abnormalities or introduce new traits holds great promise. Genetic engineering techniques offers promising pathways for precisely altering cellular genetics. Among these methodologies, clustered regularly interspaced short palindromic repeat (CRISPR), honored with 2020 Nobel Prize Chemistry, has garnered significant attention its precision editing genomes. However, CRISPR system faces challenges when applied vivo, including low delivery efficiency, off-target effects, instability. To address challenges, innovative technologies targeted precise have emerged. Engineered carrier platforms represent substantial advancement, improving stability, precision, reducing side effects associated editing. These facilitate efficient local systemic various tissues cells, immune cells. This review explores recent advances, benefits, CRISPR-based delivery. It examines carriers nanocarriers (polymeric, lipid-derived, metallic, bionanoparticles), viral particles, virus-like exosomes, providing insights into their clinical utility future prospects.

Language: Английский

Citations

5
Biomaterial-Based CRISPR/Cas9 Delivery Systems for Tumor Treatment DOI Creative Commons
Mengmeng Li, Fenglei Chen, Qian Yang

et al.

Biomaterials Research, Journal Year: 2024, Volume and Issue: 28

Published: Jan. 1, 2024

CRISPR/Cas9 gene editing technology is characterized by high specificity and efficiency, has been applied to the treatment of human diseases, especially tumors involving multiple genetic modifications. However, clinical application still faces some major challenges, most urgent which development optimized delivery vectors. Biomaterials are currently best choice for use in vectors owing their tunability, biocompatibility, efficiency. As research on biomaterial continues progress, hope system oncology therapy builds. In this review, we first detail its potential applications tumor therapy. Then, introduce different forms compare physical, viral, non-viral addition, analyze characteristics types We further review recent progress biomaterials as treat specific tumors. Finally, summarize shortcomings prospects biomaterial-based systems.

Language: Английский

Citations

4
Core-shell vector-mediated co-delivery of CRISPR/Cas9 system and hydrophobic drugs against triple-negative breast cancer stem cells DOI
Tong Wang, Tianyi Chen, Dazhao Li

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 378, P. 1080 - 1091

Published: Jan. 5, 2025

Language: Английский

Citations

0