Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing

Biologics, Год журнала: 2024, Номер Volume 18, С. 21 - 28

Опубликована: Янв. 1, 2024

Abstract: The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to wide range of genetic disorders. single-guide RNA (sgRNA) with 20-base user-defined spacer sequence Cas9 endonuclease form core CRISPR-Cas9 system. This sgRNA can direct nuclease any genomic region that includes protospacer adjacent motif (PAM) just downstream matches sequence. current challenge in clinical applications technology is potential off-target effects cause DNA cleavage at incorrect sites. Off-target genome editing confuses diminishes therapeutic addition potentially casting doubt on scientific findings regarding activities genes. In this review, we summarize recent technological advancements reducing effect editing. Keywords: CRISPR-Cas9, editing, effect, advancements, review

Язык: Английский

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CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review

Biomedicines, Год журнала: 2024, Номер 12(1), С. 238 - 238

Опубликована: Янв. 21, 2024

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing targets into distinct groups, this explores their roles cell cycle regulation, microenvironmental dynamics, interphase processes, therapy resistance reduction. The complexity CRISPR-Cas9 applications GBM research is highlighted, providing unique insights apoptosis, proliferation, immune responses within tumor microenvironment. studies challenge conventional perspectives on specific genes, emphasizing potential therapeutic implications manipulating key molecular players dynamics. Exploring GBMs yields significant regulation cellular spanning interphase, renewal, migration. Researchers, by precisely targeting uncover orchestration governing growth, differentiation during critical phases cycle. findings underscore technology unraveling complex dynamics microenvironment, offering promising avenues for targeted therapies to curb growth. also outlines addressing GBM, employing target genes associated with chemotherapy resistance, showcasing its transformative effective treatments.

Язык: Английский

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CRISPR-Cas9 in Cardiovascular Medicine: Unlocking New Potential for Treatment

Cells, Год журнала: 2025, Номер 14(2), С. 131 - 131

Опубликована: Янв. 17, 2025

Cardiovascular diseases (CVDs) remain a significant global health challenge, with many current treatments addressing symptoms rather than the genetic roots of these conditions. The advent CRISPR-Cas9 technology has revolutionized genome editing, offering transformative approach to targeting disease-causing mutations directly. This article examines potential in treatment various CVDs, including atherosclerosis, arrhythmias, cardiomyopathies, hypertension, and Duchenne muscular dystrophy (DMD). technology's ability correct single-gene high precision efficiency positions it as groundbreaking tool cardiovascular therapy. Recent developments have extended capabilities include mitochondrial critical advancement for dysfunctions often linked disorders. Despite its promise, challenges remain, off-target effects, ethical concerns, limitations delivery methods, which hinder translation into clinical practice. also explores regulatory considerations surrounding gene editing technologies, emphasizing implications somatic versus germline modifications. Future research efforts should aim enhance accuracy CRISPR-Cas9, improve systems targeted tissues, ensure safety efficacy long term. Overcoming obstacles could enable not only treat but potentially cure genetically driven diseases, heralding new era medicine health.

Язык: Английский

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CRISPR/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy

Journal of Experimental & Clinical Cancer Research, Год журнала: 2021, Номер 40(1)

Опубликована: Авг. 26, 2021

Cancer immunotherapy has gained attention as the supreme therapeutic modality for treatment of various malignancies. Adoptive T-cell therapy (ACT) is one most distinctive modalities this approach, which seeks to harness potential combating cancer cells by using autologous or allogenic tumor-specific T-cells. However, a plethora circumstances must be optimized produce functional, durable, and efficient Recently, ACT been further realized introduction novel gene-editing platforms such CRISPR/Cas9 system; technique utilized create T-cells furnished with recombinant receptor (TCR) chimeric antigen (CAR) that have precise tumor recognition, minimal side effects treatment-related toxicities, robust proliferation cytotoxicity, nominal exhaustion. Here, we aim review categorize recent breakthroughs genetically modified TCR/CAR through technology address pearls pitfalls each method. In addition, investigate latest ongoing clinical trials are applying CRISPR-associated cancers.

Язык: Английский

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A Review on Advanced CRISPR-Based Genome-Editing Tools: Base Editing and Prime Editing

Molecular Biotechnology, Год журнала: 2022, Номер 65(6), С. 849 - 860

Опубликована: Дек. 22, 2022

Язык: Английский

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Biomedical applications of nanomaterials in the advancement of nucleic acid therapy: Mechanistic challenges, delivery strategies, and therapeutic applications

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 241, С. 124582 - 124582

Опубликована: Апрель 26, 2023

Язык: Английский

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Genome Editing and Improvement of Abiotic Stress Tolerance in Crop Plants

Life, Год журнала: 2023, Номер 13(7), С. 1456 - 1456

Опубликована: Июнь 27, 2023

Genome editing aims to revolutionise plant breeding and could assist in safeguarding the global food supply. The inclusion of a 12–40 bp recognition site makes mega nucleases first tools utilized for genome generation gene-editing tools. Zinc finger (ZFNs) are second technique, because they create double-stranded breaks, more dependable effective. ZFNs were original designed nuclease-based approach editing. Cys2-His2 zinc domain’s discovery made this technique possible. Clustered regularly interspaced short palindromic repeats (CRISPR) improve genetics, boost biomass production, increase nutrient usage efficiency, develop disease resistance. Plant genomes can be effectively modified using genome-editing technologies enhance characteristics without introducing foreign DNA into genome. Next-generation will soon defined by these exact methods. There is abroad promise that genome-edited crops essential years come improving sustainability climate-change resilience systems. This method also has great potential enhancing crops’ resistance various abiotic stressors. In review paper, we summarize most recent findings about mechanism stress response crop plants use CRISPR/Cas mediated systems tolerance stresses including drought, salinity, cold, heat, heavy metals.

Язык: Английский

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Advances in environmental biotechnology with CRISPR/Cas9: bibliometric review and cutting-edge applications

Deleted Journal, Год журнала: 2025, Номер 7(3)

Опубликована: Фев. 22, 2025

Язык: Английский

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Advance trends in targeting homology-directed repair for accurate gene editing: An inclusive review of small molecules and modified CRISPR-Cas9 systems

Bioimpacts, Год журнала: 2022, Номер 12(4), С. 371 - 391

Опубликована: Июнь 20, 2022

Introduction: Clustered regularly interspaced short palindromic repeat and its associated protein (CRISPR-Cas)-based technologies generate targeted modifications in host genome by inducing site-specific double-strand breaks (DSBs) that can serve as a substrate for homology-directed repair (HDR) both vitro vivo models. HDR pathway could enhance incorporation of exogenous DNA templates into the CRISPR-Cas9-mediated DSB site. Owing to low rate pathway, efficiency accurate editing is diminished. Enhancing provide fast, easy, based on CRISPR-Cas9 technologies. Methods: The current study presents an overview attempts conducted precise strategies small molecules modified systems. Results: In order increase cells, several logical have been introduced such generating CRISPR effector chimeric proteins, anti-CRISPR Cas9 with donor template, using validated synthetic or natural either inhibiting non-homologous end joining (NHEJ), stimulating HDR, synchronizing cell cycle. Recently, high-throughput screening methods applied identification which along system regulate through HDR. Conclusion: stimulation components NHEJ accuracy CRISPR-Cas-mediated engineering Generating programmable endonucleases this opportunity direct template close proximity DSB. Small their derivatives also proficiently block activate certain pathways bring up novel perspectives increasing efficiency, especially human cells. Further, high throughput molecule libraries result more discoveries promising chemicals improve

Язык: Английский

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Gene Therapy Targeting PCSK9

Metabolites, Год журнала: 2022, Номер 12(1), С. 70 - 70

Опубликована: Янв. 12, 2022

The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include inhibition proprotein convertase subtilisin/kexin type 9 (PCSK9) with monoclonal antibodies, small interfering RNA and antisense drugs. cumulative effects LDL cholesterol on atherosclerosis make early, potent, long-term reductions desirable-ideally without need regular intake or application medication importantly, side effects. Current reports show durable primates following one single PCSK9 gene base editors. Use CRISPR/Cas system enables precise genome editing down to single-nucleotide changes. Provided safety documentation a reduction events, this novel technique has potential fundamentally change our current concepts prevention. In review, is explained state vivo approaches presented.

Язык: Английский

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