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

@article{Musunuru2021InVC,
  title={In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates.},
  author={Kiran Musunuru and Alexandra C. Chadwick and Taiji Mizoguchi and S. P{\'e}rez Garc{\'i}a and Jamie E. DeNizio and Caroline W Reiss and Kui Wang and Sowmya Iyer and Chaitali Dutta and Victoria Clendaniel and Michael Amaonye and Aaron Beach and Kathleen Berth and Souvik Biswas and Maurine C Braun and Huei-Mei Chen and Thomas V. Colace and John Ganey and Soumyashree A. Gangopadhyay and Ryan Garrity and Lisa N. Kasiewicz and Jennifer Lavoie and James A. Madsen and Yuri Matsumoto and Anne Marie Mazzola and Yusuf Nasrullah and Joseph Nneji and Huilan Ren and Athul Sanjeev and Madeleine Shay and Mary R. Stahley and Steven H.Y. Fan and Ying K. Tam and Nicole M. Gaudelli and Giuseppe Ciaramella and Leslie E. Stolz and Padma Malyala and Christopher J. Cheng and Kallanthottathil G Rajeev and Ellen Rohde and Andrew M. Bellinger and Sekar Kathiresan},
  journal={Nature},
  year={2021},
  volume={593 7859},
  pages={
          429-434
        }
}
Gene-editing technologies, which include the CRISPR-Cas nucleases1-3 and CRISPR base editors4,5, have the potential to permanently modify disease-causing genes in patients6. The demonstration of durable editing in target organs of nonhuman primates is a key step before in vivo administration of gene editors to patients in clinical trials. Here we demonstrate that CRISPR base editors that are delivered in vivo using lipid nanoparticles can efficiently and precisely modify disease-related genes… 
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Use of the CRISPR/Cas system enables precise genome editing down to single-nucleotide changes and has the potential to fundamentally change current concepts of cardiovascular prevention.
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TLDR
An overview of CRISPR technology is provided, with a particular focus on recent studies with relevance to its potential use in atherosclerotic cardiovascular disease.
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TLDR
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TLDR
In vivo delivery of Nme2-ABE and its guide RNA by a single-AAV vector can efficiently edit mouse genomic loci and revert the disease mutation and phenotype in an adult mouse model of tyrosinemia.
Innovations in CRISPR-Based Therapies
  • G. Kesavan
  • Biology, Medicine
    Molecular Biotechnology
  • 2021
TLDR
This mini-review assesses the status of CRISPR-based therapies, both in vivo and ex vivo, and the challenges associated with clinical translation and the safety, affordability, and feasibility ofCRISPR therapies.
The use of new CRISPR tools in cardiovascular research and medicine
TLDR
How these novel CRISPR tools are used to investigate biological processes and disease pathophysiology for cardiovascular research and medicine and the prospect of therapeutic genome editing by CRISpr tools to cure genetic cardiovascular diseases are described.
In vivo somatic cell base editing and prime editing.
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TLDR
Genome editing with the CRISPR–CRISPR-associated 9 system disrupts the Pcsk9 gene in vivo with high efficiency and reduces blood cholesterol levels in mice, which may have therapeutic potential for the prevention of cardiovascular disease in humans.
Treatment of a metabolic liver disease by in vivo genome base editing in adult mice
TLDR
AAV-mediated base editing corrects an autosomal recessive mutation in the Pahenu2 gene and ameliorates molecular deficits in a mouse model of metabolic liver disease and suggests that targeting genetic diseases in vivo using AAV-mediated delivery of base-editing agents is feasible.
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TLDR
This work identifies regions of sgRNA that can be modified while maintaining or enhancing genome-editing activity, and develops an optimal set of chemical modifications for in vivo applications, and shows that a single intravenous injection into mice induces >80% editing of Pcsk9 in the liver.
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TLDR
The results of this proof-of-concept work demonstrate the possibility of efficiently performing gene editing before birth, pointing to a potential new therapeutic approach for selected congenital genetic disorders.
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TLDR
The ability to precisely introduce therapeutically relevant nucleotide variants into the genome in somatic tissues in adult mammals is demonstrated, highlighting a potentially safer alternative to therapeutic genome editing.
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TLDR
It is shown in a mouse model of tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) can correct an A>G splice-site mutation.
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TLDR
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