In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates

Nature, Journal Year: 2021, Volume and Issue: 593(7859), P. 429 - 434

Published: May 19, 2021

Language: Английский

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Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(6), P. 895 - 905

Published: April 12, 2021

Language: Английский

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Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins

Cell, Journal Year: 2022, Volume and Issue: 185(2), P. 250 - 265.e16

Published: Jan. 1, 2022

Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package base editor or Cas9 ribonucleoproteins. By engineering VLPs overcome cargo packaging, release, localization bottlenecks, we developed fourth-generation eVLPs mediate efficient several primary mouse human cell types. Using different glycoproteins alters their cellular tropism. Single injections into mice support therapeutic levels multiple tissues, reducing serum Pcsk9 78% following 63% liver editing, partially restoring visual function a model genetic blindness. In vitro off-target from was virtually undetected, an improvement AAV plasmid delivery. These results establish promising vehicles for macromolecule combine key both viral nonviral

Language: Английский

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CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors

Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 136 - 150

Published: April 1, 2020

Language: Английский

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Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 40(5), P. 731 - 740

Published: Dec. 9, 2021

Language: Английский

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Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs

Nature Reviews Materials, Journal Year: 2023, Volume and Issue: 8(4), P. 282 - 300

Published: Jan. 19, 2023

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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Engineered miniature CRISPR-Cas system for mammalian genome regulation and editing

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(20), P. 4333 - 4345.e4

Published: Sept. 3, 2021

Compact and versatile CRISPR-Cas systems will enable genome engineering applications through high-efficiency delivery in a wide variety of contexts. Here, we create an efficient miniature Cas system (CasMINI) engineered from the type V-F Cas12f (Cas14) by guide RNA protein engineering, which is less than half size currently used CRISPR (Cas9 or Cas12a). We demonstrate that CasMINI can drive high levels gene activation (up to thousands-fold increases), while natural fails function mammalian cells. show has comparable activities Cas12a for activation, highly specific, allows robust base editing editing. expect be broadly useful cell therapy ex vivo vivo.

Language: Английский

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Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing ofAngptl3

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(10)

Published: March 1, 2021

Significance Genome editing technologies enable the permanent repair of disease-causing genetic mutations. However, application this technology has been limited by technical challenge achieving safe, effective, and specific in vivo delivery CRISPR-Cas9 genome components. Here, we report development a newly identified lipid nanoparticle (LNP) for mRNA to liver. While LNPs have FDA approved siRNA liver, here examine their editing. When compared head-to-head, our platform significantly outperforms FDA-approved LNP efficient Cas9 knockdown Angptl3 gene subsequent regulation hypercholesterolemia, while matching safety specificity platform.

Language: Английский

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Strategic vision for improving human health at The Forefront of Genomics

Nature, Journal Year: 2020, Volume and Issue: 586(7831), P. 683 - 692

Published: Oct. 28, 2020

Language: Английский

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