Recent Advances in Genome-Editing Technology with CRISPR/Cas9 Variants and Stimuli-Responsive Targeting Approaches within Tumor Cells: A Future Perspective of Cancer Management DOI Open Access
Khaled S. Allemailem, Saleh A. Almatroodi, Ahmad Almatroudi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7052 - 7052

Published: April 11, 2023

The innovative advances in transforming clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) into different variants have taken the art of genome-editing specificity to new heights. Allosteric modulation Cas9-targeting by sgRNA sequence alterations and protospacer adjacent motif (PAM) modifications been a good lesson learn about activity scores Cas9 variants. Some high-fidelity ranked as Sniper-Cas9, eSpCas9 (1.1), SpCas9-HF1, HypaCas9, xCas9, evoCas9. However, selection an ideal variant for given target remains challenging task. A safe efficient delivery system CRISPR/Cas9 complex at tumor sites faces considerable challenges, nanotechnology-based stimuli-responsive approaches significantly contributed cancer management. Recent innovations nanoformulation design, such pH, glutathione (GSH), photo, thermal, magnetic responsive systems, modernized approaches. These nanoformulations possess enhanced cellular internalization, endosomal membrane disruption/bypass, controlled release. In this review, we aim elaborate on specific endonuclease system. Furthermore, critical constraints clinical translations towards management prospects are described.

Language: Английский

Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation DOI Creative Commons
John J. Chen,

Diane Nathaniel,

Preethi Raghavan

et al.

Journal of Biological Chemistry, Journal Year: 2019, Volume and Issue: 294(50), P. 18952 - 18966

Published: Oct. 2, 2019

Intercellular propagation of protein aggregation is emerging as a key mechanism in the progression several neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia (FTD). However, we lack systematic understanding cellular pathways controlling prion-like aggregation. To uncover such pathways, here performed CRISPR interference (CRISPRi) screens human cell-based model tau monitored by FRET. Our uncovered that knockdown components endosomal sorting complexes required for transport (ESCRT) machinery, charged multivesicular body 6 (CHMP6), or CHMP2A combination with CHMP2B (whose gene linked to familial FTD), promote We found knocking down genes encoding these proteins also causes damage endolysosomal membranes, consistent role ESCRT pathway membrane repair. Leakiness compartment significantly enhanced aggregation, likely making seeds more available pools cytoplasmic tau. Together, findings suggest escape critical step diseases. Leaky endosomes push over seed limitJournal Biological ChemistryVol. 294Issue 50PreviewThe inter- intracellular aggregated like central behind various The steps which aggregates propagates currently unclear. Chen et al. now combine genetic screen identify complex machinery mediators aggregates. Full-Text PDF Open Access

Language: Английский

Citations

144
Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases DOI Creative Commons

Shaoshuai Wu,

Qing-Cui Li,

Changqing Yin

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(10), P. 4374 - 4382

Published: Jan. 1, 2020

CRISPR/Cas genome editing is a simple, cost effective, and highly specific technique for introducing genetic variations.In mammalian cells, can facilitate non-homologous end joining, homologydirected repair, single-base exchanges.Cas9/Cas12a nuclease, dCas9 transcriptional regulators, base editors, PRIME editors RNA tools are widely used in basic research.Currently, variety of CRISPR/Cas-based therapeutics being investigated clinical trials.Among many new findings that have advanced the field, we highlight few recent advances relevant to gene therapies monogenic human diseases.

Language: Английский

Citations

115
Dead Cas Systems: Types, Principles, and Applications DOI Open Access
Sergey Brezgin, Anastasiya Kostyusheva, Dmitry Kostyushev

et al.

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(23), P. 6041 - 6041

Published: Nov. 30, 2019

The gene editing tool CRISPR-Cas has become the foundation for developing numerous molecular systems used in research and, increasingly, medical practice. In particular, Cas proteins devoid of nucleolytic activity (dead proteins; dCas) can be to deliver functional cargo programmed sites genome. this review, we describe current CRISPR different dCas-based approaches and summarize their most significant applications. We conclude with comments on state-of-art field future directions.

Language: Английский

Citations

102
Long noncoding RNA: a dazzling dancer in tumor immune microenvironment DOI Creative Commons
Yalu Zhang, Qiaofei Liu, Quan Liao

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Nov. 4, 2020

Abstract Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding that highly linked to various cellular functions and pathological process. Emerging evidence indicates lncRNAs participate in crosstalk between tumor stroma, reprogramming immune microenvironment (TIME). TIME possesses distinct populations myeloid cells lymphocytes influence the escape cancer, response immunotherapy, survival patients. However, hitherto, comprehensive review aiming at relationship is missing. In this review, we focus on functional roles molecular mechanisms within TIME. Furthermore, discussed potential immunotherapeutic strategies based their limitations.

Language: Английский

Citations

91
Strategies for controlling CRISPR/Cas9 off-target effects and biological variations in mammalian genome editing experiments DOI

Michelle L. Kimberland,

Wangfang Hou,

Adolfo Alfonso-Pecchio

et al.

Journal of Biotechnology, Journal Year: 2018, Volume and Issue: 284, P. 91 - 101

Published: Aug. 22, 2018

Language: Английский

Citations

86
CRISPR/dCas-mediated transcriptional and epigenetic regulation in plants DOI Creative Commons
Changtian Pan, Simon Sretenovic, Yiping Qi

et al.

Current Opinion in Plant Biology, Journal Year: 2021, Volume and Issue: 60, P. 101980 - 101980

Published: Jan. 2, 2021

Language: Английский

Citations

86
Improving CRISPR Genome Editing by Engineering Guide RNAs DOI

Su Bin Moon,

Do Yon Kim,

Jeong‐Heon Ko

et al.

Trends in biotechnology, Journal Year: 2019, Volume and Issue: 37(8), P. 870 - 881

Published: March 4, 2019

Language: Английский

Citations

82
CRISPR/Cas9 – An evolving biological tool kit for cancer biology and oncology DOI Creative Commons
Xueli Tian, Tingxuan Gu,

Satyananda Patel

et al.

npj Precision Oncology, Journal Year: 2019, Volume and Issue: 3(1)

Published: March 18, 2019

Abstract The development of genetic engineering in the 1970s marked a new frontier genome-editing technology. Gene-editing technologies have provided plethora benefits to life sciences. c lustered r egularly i nterspaced s hort p alindromic epeats/CRISPR associated protein 9 (CRISPR/ Cas9) system is versatile technology that provides ability add or remove DNA genome sequence-specific manner. Serious efforts are underway improve efficiency CRISPR/Cas9 targeting and thus reduce off-target effects. Currently, various applications used cancer biology oncology perform robust site-specific gene editing, thereby becoming more useful for biological clinical applications. Many variants being rapidly developed. Experimental approaches based on CRISPR created very promising tool inexpensive simple developing effective therapeutics. This review discusses diverse CRISPR-based gene-editing tools potential future therapies.

Language: Английский

Citations

80
Intellectual disability genomics: current state, pitfalls and future challenges DOI Creative Commons
Nuno Maia, Maria João Nabais Sá, Manuel Melo Pires

et al.

BMC Genomics, Journal Year: 2021, Volume and Issue: 22(1)

Published: Dec. 20, 2021

Abstract Intellectual disability (ID) can be caused by non-genetic and genetic factors, the latter being responsible for more than 1700 ID-related disorders. The broad ID phenotypic heterogeneity, as well difficulty in establishment of inheritance pattern, often result a delay diagnosis. It has become apparent that massive parallel sequencing overcome these difficulties. In this review we address: (i) aetiology, (ii) clinical/medical settings testing, (iii) sequencing, (iv) variant filtering prioritization, (v) classification guidelines functional studies, (vi) diagnostic yield. Furthermore, need constant update methodologies tests, is essential. Thus, international collaborations, to gather expertise, data resources through multidisciplinary contributions, are fundamental keep track fast progress gene discovery.

Language: Английский

Citations

57
Emerging Therapies and Novel Targets for TDP-43 Proteinopathy in ALS/FTD DOI Creative Commons
Lindsey R. Hayes, Petr Kaláb

Neurotherapeutics, Journal Year: 2022, Volume and Issue: 19(4), P. 1061 - 1084

Published: July 1, 2022

Language: Английский

Citations

42