Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease DOI Creative Commons
Martijn P. T. Ernst, Mike Broeders,

Pablo Herrero-Hernandez

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2020, Volume and Issue: 18, P. 532 - 557

Published: July 4, 2020

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, is applied ex vivo in T cells, transgenic cell receptor (tTCR)-T chimeric antigen (CAR)-T cells to improve adoptive therapy for multiple types. This involves knockouts immune checkpoint regulators such as PD-1, components endogenous TCR histocompatibility leukocyte (HLA) complex generate universal allogeneic CAR-T CD7 prevent self-destruction therapy. cervix carcinoma caused by human papillomavirus (HPV), E6 E7 genes are disrupted topically machinery. HIV infection, CCR5 co-receptor HIV-resistant hematopoietic stem cells. β-thalassemia sickle disease, engineered induce production fetal hemoglobin. AAV-mediated exploit liver systemic therapeutic proteins hemophilia mucopolysaccharidoses, eye restore splicing CEP920 Leber's congenital amaurosis. Close consideration safety aspects education stakeholders will be essential a successful implementation technology clinic.

Language: Английский

Genome Edited Crops Touch the Market: A View on the Global Development and Regulatory Environment DOI Creative Commons

Jochen Menz,

Dominik Modrzejewski, Frank Hartung

et al.

Frontiers in Plant Science, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 9, 2020

Products of genome editing as the most promising "New Plant Breeding Technology" (NPBT) have made transition from lab to market in a short time. Globally, research activities employing are constantly expanding and more plants with market-oriented traits being developed, while companies already released first genome-edited crops market. Few countries, which located Americas, adapted legislations these technologies or guidelines supporting use editing. Other countries debating path come either because there is no clarity on legal classification due consensus hampered by renewed GMO debate. In recent years (2017 - 2020), eight introduced clarifying status edited products many those actively committed international harmonization their policies. this publication we give an overview current potentially future regulatory environment update derived oriented traits.

Language: Английский

Citations

200
Inorganic arsenic toxicity and alleviation strategies in rice DOI Creative Commons

Amos Musyoki Mawia,

Suozhen Hui,

Liang Zhou

et al.

Journal of Hazardous Materials, Journal Year: 2020, Volume and Issue: 408, P. 124751 - 124751

Published: Dec. 16, 2020

Direct or indirect exposure to inorganic arsenic (iAs) in the forms of AsIII (arsenite) and AsV (arsenate) through consumption As-contaminated food materials drinking water leads poisoning. Rice (Oryza sativa L.) plant potentially accumulates a high amount iAs from paddy fields than any other cereal crops. This makes it be major source especially among population that uses as their dominant diet. The accumulation As human bodies poses serious global health risk population. Various conventional methods have been applied reduce rice plant. However, success rate these techniques is low. Therefore, development efficient effective aimed at lowering toxicity very crucial public concern. With current advancement technology, new strategies addressing this concern are being developed utilized various parts world. In review, we discuss recent advances management plants emphasizing use nanotechnology biotechnology approaches. Also, prospects challenges facing approaches described.

Language: Английский

Citations

177
CRISPR/dCas9 platforms in plants: strategies and applications beyond genome editing DOI Creative Commons
Mahdi Moradpour,

Siti Nor Akmar Abdulah

Plant Biotechnology Journal, Journal Year: 2019, Volume and Issue: 18(1), P. 32 - 44

Published: Aug. 8, 2019

Summary Clustered regularly interspaced short palindromic repeat ( CRISPR ) and Cas9‐associated protein systems provide a powerful genetic manipulation tool that can drive plant research forward. Nuclease‐dead Cas9 dC as9) is an enzymatically inactive mutant of in which its endonuclease activity non‐functional. The applications / as9 have expanded diversified recent years. Originally, was used as /Cas9 re‐engineering enables targeted expression any gene or multiple genes through recruitment transcriptional effector domains without introducing irreversible DNA ‐damaging mutations. Subsequent made use ability to recruit modifying enzymes reporter proteins target sites. In this paper, the most progress plants, include activation repression, epigenome editing, modulation chromatin topology, live‐cell imaging ‐free modification, will be reviewed. associated strategies for exploiting system crop improvement with dimer future functional genomics crops development traits briefly discussed.

Language: Английский

Citations

158
CRISPR-based genome editing through the lens of DNA repair DOI Creative Commons

Tarun S. Nambiar,

Lou Baudrier,

Pierre Billon

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(2), P. 348 - 388

Published: Jan. 1, 2022

Language: Английский

Citations

155
Precision genome editing using cytosine and adenine base editors in mammalian cells DOI
Tony P. Huang, Gregory A. Newby, David R. Liu

et al.

Nature Protocols, Journal Year: 2021, Volume and Issue: 16(2), P. 1089 - 1128

Published: Jan. 18, 2021

Language: Английский

Citations

121
Modular (de)construction of complex bacterial phenotypes by CRISPR/nCas9-assisted, multiplex cytidine base-editing DOI Creative Commons
Daniel C. Volke, Román A. Martino, Ekaterina Kozaeva

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 31, 2022

Abstract CRISPR/Cas technologies constitute a powerful tool for genome engineering, yet their use in non-traditional bacteria depends on host factors or exogenous recombinases, which limits both efficiency and throughput. Here we mitigate these practical constraints by developing widely-applicable engineering toolset Gram-negative bacteria. The challenge is addressed tailoring CRISPR base editor that enables single-nucleotide resolution manipulations (C·G → T·A) with >90% efficiency. Furthermore, incorporating Cas6-mediated processing of guide RNAs streamlined protocol plasmid assembly supports multiplex editing >85% adopted to construct deconstruct complex phenotypes the soil bacterium Pseudomonas putida . Single-step an aromatic-compound production phenotype multi-step deconstruction intricate redox metabolism illustrate versatility afforded our toolbox. Hence, this approach overcomes typical limitations previous empowers programs were out reach thus far.

Language: Английский

Citations

77
Precise genome-editing in human diseases: mechanisms, strategies and applications DOI Creative Commons

Yanjiang Zheng,

Yifei Li, Kaiyu Zhou

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 26, 2024

Precise genome-editing platforms are versatile tools for generating specific, site-directed DNA insertions, deletions, and substitutions. The continuous enhancement of these has led to a revolution in the life sciences, which promises deliver novel therapies genetic disease. can be traced back 1950s with discovery DNA's double-helix and, after 70 years development, evolved from crude vitro applications wide range sophisticated capabilities, including vivo applications. Nonetheless, precise faces constraints such as modest efficiency, delivery challenges, off-target effects. In this review, we explore genome-editing, focus on introduction landmark events its history, various platforms, systems, First, discuss history genome-editing. Second, describe current state strategies explain how techniques offer unprecedented precision versatility modifying human genome. Third, introduce systems used deploy components through DNA, RNA, RNPs. Finally, summarize labeling endogenous genes, screening variants, molecular recording, disease models, gene therapy, ex therapy potential future advances.

Language: Английский

Citations

18
Target-Site Mutations Conferring Herbicide Resistance DOI Creative Commons

Brent Murphy,

Patrick J. Tranel

Plants, Journal Year: 2019, Volume and Issue: 8(10), P. 382 - 382

Published: Sept. 28, 2019

Mutations conferring evolved herbicide resistance in weeds are known nine different sites of action. This review summarizes recently reported resistance-conferring mutations for each these target sites. One emerging trend is an increase reports multiple mutations, including amino acid changes at the glyphosate site, as well involving two nucleotide a single codon. Standard reference sequences suggested which standards do not already exist. We also discuss experimental approaches investigating cross-resistance patterns and fitness costs specific target-site mutations.

Language: Английский

Citations

129
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
Sharpening the Molecular Scissors: Advances in Gene-Editing Technology DOI Creative Commons
Mike Broeders,

Pablo Herrero-Hernandez,

Martijn P. T. Ernst

et al.

iScience, Journal Year: 2019, Volume and Issue: 23(1), P. 100789 - 100789

Published: Dec. 19, 2019

The ability to precisely modify human genes has been made possible by the development of tools such as meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas. These now make it generate targeted deletions, insertions, gene knock outs, point variants; modulate expression targeting transcription factors or epigenetic machineries DNA; target RNA. Endogenous repair mechanisms are used modifications required in they include non-homologous end joining, homology-directed repair, homology-independent integration, microhomology-mediated base-excision mismatch repair. Off-target effects can be monitored using silico prediction sequencing minimized Cas proteins with higher accuracy, high-fidelity Cas9, enhanced-specificity hyperaccurate Cas9. Alternatives Cas9 have identified, including Cpf1, Cas12a, Cas12b, smaller orthologs CjCas9. Delivery gene-editing components is performed ex vivo standard techniques AAV, lipid nanoparticles, cell-penetrating peptides. Clinical technology progressing several fields, immunotherapy cancer treatment, antiviral therapy for HIV infection, treatment genetic disorders β-thalassemia, sickle cell disease, lysosomal storage disorders, retinal dystrophy. Here we review these technological advances challenges their clinical implementation.

Language: Английский

Citations

92