Gene editing and CRISPR in the clinic: current and future perspectives DOI Open Access
Matthew P. Hirakawa, Raga Krishnakumar, Jerilyn A. Timlin

et al.

Bioscience Reports, Journal Year: 2020, Volume and Issue: 40(4)

Published: March 24, 2020

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most use of to date has focused ex vivo gene cells followed by their re-introduction back the patient. The approach is highly effective for many disease states, including cancers sickle cell disease, but ideally genome would also be applied diseases which require modification in vivo. However, technologies can confounded problems such as off-target editing, inefficient or delivery, stimulation counterproductive immune responses. Current research addressing these issues may provide new opportunities space. In this review, we examine current status scientific basis trials featuring ZFNs, TALENs, CRISPR-based known limitations humans, developing engineering space that should lay groundwork further translation application.

Language: Английский

Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors DOI
Andrew V. Anzalone, Luke W. Koblan, David R. Liu

et al.

Nature Biotechnology, Journal Year: 2020, Volume and Issue: 38(7), P. 824 - 844

Published: June 22, 2020

Language: Английский

Citations

1799
Deciphering cell–cell interactions and communication from gene expression DOI Open Access
Erick Armingol, Adam Officer, Olivier Harismendy

et al.

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(2), P. 71 - 88

Published: Nov. 9, 2020

Language: Английский

Citations

914
Detection of unamplified target genes via CRISPR–Cas9 immobilized on a graphene field-effect transistor DOI
Reza Hajian, Sarah Balderston,

Thanhtra P. Tran

et al.

Nature Biomedical Engineering, Journal Year: 2019, Volume and Issue: 3(6), P. 427 - 437

Published: March 25, 2019

Language: Английский

Citations

543
Predictable and precise template-free CRISPR editing of pathogenic variants DOI
Max W. Shen, Mandana Arbab, Jonathan Y. Hsu

et al.

Nature, Journal Year: 2018, Volume and Issue: 563(7733), P. 646 - 651

Published: Nov. 1, 2018

Language: Английский

Citations

519
Directed Evolution: Methodologies and Applications DOI
Yajie Wang, Pu Xue, Mingfeng Cao

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(20), P. 12384 - 12444

Published: July 23, 2021

Directed evolution aims to expedite the natural process of biological molecules and systems in a test tube through iterative rounds gene diversifications library screening/selection. It has become one most powerful widespread tools for engineering improved or novel functions proteins, metabolic pathways, even whole genomes. This review describes commonly used diversification strategies, screening/selection methods, recently developed continuous strategies directed evolution. Moreover, we highlight some representative applications nucleic acids, genetic circuits, viruses, cells. Finally, discuss challenges future perspectives

Language: Английский

Citations

453
Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities DOI
Sarah J. Tabrizi, Michael Flower, Christopher A. Ross

et al.

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 16(10), P. 529 - 546

Published: Aug. 14, 2020

Language: Английский

Citations

398
PnB Designer: a web application to design prime and base editor guide RNAs for animals and plants DOI Creative Commons
Sebastian M. Siegner, Mehmet E. Karasu, Markus Schröder

et al.

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

Published: March 2, 2021

Abstract Background The rapid expansion of the CRISPR toolbox through tagging effector domains to either enzymatically inactive Cas9 (dCas9) or nickase (nCas9) has led several promising new gene editing strategies. Recent additions include cytosine adenine base editors (CBEs and ABEs) prime (PEs), in which a deaminase reverse transcriptase are fused nCas9, respectively. These tools hold great promise model correct disease-causing mutations animal plant models. But so far, no widely-available exist automate design both BE PE reagents. Results We developed PnB Designer, web-based application for pegRNAs PEs guide RNAs BEs. Designer makes it easy targeting single multiple targets on variant reference genome from organisms spanning kingdoms. With we designed all known disease causing available ClinVar. Additionally, can be used install revert SNV, scanning with one CBE seven different ABE PAM variants returning best use. is publicly accessible at http://fgcz-shiny.uzh.ch/PnBDesigner/ Conclusion created user-friendly tool reagents, should simplify choosing strategy avoiding complications.

Language: Английский

Citations

333
CRISPR in cancer biology and therapy DOI Open Access
Alyna Katti, Bianca J. Diaz, Christina M. Caragine

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(5), P. 259 - 279

Published: Feb. 22, 2022

Language: Английский

Citations

296
Disease modelling in human organoids DOI Creative Commons
Madeline A. Lancaster, Meritxell Huch

Disease Models & Mechanisms, Journal Year: 2019, Volume and Issue: 12(7)

Published: July 1, 2019

ABSTRACT The past decade has seen an explosion in the field of vitro disease modelling, particular development organoids. These self-organizing tissues derived from stem cells provide a unique system to examine mechanisms ranging organ homeostasis and disease. Because organoids develop according intrinsic developmental programmes, resultant tissue morphology recapitulates architecture with remarkable fidelity. Furthermore, fact that these can be human progenitors allows for study uniquely processes disorders. This article accompanying poster highlight currently available methods, particularly those aimed at modelling biology, overview their capabilities limitations. We also speculate on possible future technological advances have potential great strides both regenerative strategies.

Language: Английский

Citations

295
CRISPR-Cas9 DNA Base-Editing and Prime-Editing DOI Open Access

Ariel Kantor,

Michelle E. McClements, Robert E. MacLaren

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6240 - 6240

Published: Aug. 28, 2020

Many genetic diseases and undesirable traits are due to base-pair alterations in genomic DNA. Base-editing, the newest evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based technologies, can directly install point-mutations cellular DNA without inducing a double-strand break (DSB). Two classes base-editors have been described thus far, cytosine (CBEs) adenine (ABEs). Recently, prime-editing (PE) has further expanded CRISPR-base-edit toolkit all twelve possible transition transversion mutations, as well small insertion or deletion mutations. Safe efficient delivery editing systems target cells is one most paramount challenging components for therapeutic success BEs. Due its broad tropism, well-studied serotypes, reduced immunogenicity, adeno-associated vector (AAV) emerged leading platform viral genome agents, including DNA-base-editors. In this review, we describe development various base-editors, assess their technical advantages limitations, discuss potential treat debilitating human diseases.

Language: Английский

Citations

292