CRISPR technology: A decade of genome editing is only the beginning

Science, Journal Year: 2023, Volume and Issue: 379(6629)

Published: Jan. 19, 2023

The advent of clustered regularly interspaced short palindromic repeat (CRISPR) genome editing, coupled with advances in computing and imaging capabilities, has initiated a new era which genetic diseases individual disease susceptibilities are both predictable actionable. Likewise, genes responsible for plant traits can be identified altered quickly, transforming the pace agricultural research breeding. In this Review, we discuss current state CRISPR-mediated manipulation human cells, animals, plants along relevant successes challenges present roadmap future technology.

Language: Английский

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High-content CRISPR screening

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Feb. 10, 2022

Language: Английский

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Therapeutic in vivo delivery of gene editing agents

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2806 - 2827

Published: July 1, 2022

In vivo gene editing therapies offer the potential to treat root causes of many genetic diseases. Realizing promise therapeutic in requires ability safely and efficiently deliver agents relevant organs tissues vivo. Here, we review current delivery technologies that have been used enable editing, including viral vectors, lipid nanoparticles, virus-like particles. Since no single modality is likely be appropriate for every possible application, compare benefits drawbacks each method highlight opportunities future improvements.

Language: Английский

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Engineering the next generation of cell-based therapeutics

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(9), P. 655 - 675

Published: May 30, 2022

Language: Английский

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High-content CRISPR screening

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Feb. 10, 2022

Language: Английский

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Spatial genomics enables multi-modal study of clonal heterogeneity in tissues

Nature, Journal Year: 2021, Volume and Issue: 601(7891), P. 85 - 91

Published: Dec. 15, 2021

Language: Английский

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Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases

Science Advances, Journal Year: 2022, Volume and Issue: 8(37)

Published: Sept. 14, 2022

CRISPR-Cas9 gene editing has emerged as a powerful therapeutic technology, but the lack of safe and efficient in vivo delivery systems, especially for tissue-specific vectors, limits its broad clinical applications. Delivery Cas9 ribonucleoprotein (RNP) owns competitive advantages over other options; however, large size RNPs exceeds loading capacity currently available vectors. Here, we report previously unidentified genome system, named exosome RNP , which were loaded into purified exosomes isolated from hepatic stellate cells through electroporation. Exosome facilitated effective cytosolic vitro while specifically accumulated liver tissue vivo. showed vigorous potential acute injury, chronic fibrosis, hepatocellular carcinoma mouse models via targeting p53 up-regulated modulator apoptosis ( PUMA ), cyclin E1 CcnE1 K (lysine) acetyltransferase 5 KAT5 respectively. The developed provides feasible platform precise therapies diseases.

Language: Английский

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Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering

Cell Reports, Journal Year: 2021, Volume and Issue: 35(9), P. 109207 - 109207

Published: June 1, 2021

Language: Английский

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Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 7(7), P. 887 - 900

Published: Jan. 12, 2023

Language: Английский

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Dual-AAV delivering split prime editor system for in vivo genome editing

Molecular Therapy, Journal Year: 2021, Volume and Issue: 30(1), P. 283 - 294

Published: July 21, 2021

Prime editor (PE), a new genome editing tool, can generate all 12 possible base-to-base conversions, insertion, and deletion of short fragment DNA. PE has the potential to correct majority known human genetic disease-related mutations. Adeno-associated viruses (AAVs), safe vector widely used in clinics, are not capable delivering (∼6.3 kb) single because limited loading capacity (∼4.8 kb). To accommodate AAVs, we constructed four split-PE (split-PE994, split-PE1005, split-PE1024, split-PE1032) using Rma intein (Rhodothermus marinus). With use GFP-mutated reporter system, reconstituting activities were screened, two efficient split-PEs (split-PE1005 split-PE1024) identified. We then demonstrated that delivered by dual-AAV1, especially could mediate base transversion insertion at endogenous sites cells. test performance vivo, split-PE1024 was into adult mouse retina dual-AAV8. successful Dnmt1 retina. Our study provides method deliver tissue, paving way for vivo gene-editing therapy PE.

Language: Английский

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