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 PMID:34665130  

5'-Modifications improve potency and efficacy of DNA donors for precision genome editing.

Krishna S Ghanta | Zexiang Chen | Aamir Mir | Gregoriy A Dokshin | Pranathi M Krishnamurthy | Yeonsoo Yoon | Judith Gallant | Ping Xu | Xiao-Ou Zhang | Ahmet Rasit Ozturk | Masahiro Shin | Feston Idrizi | Pengpeng Liu | Hassan Gneid | Alireza Edraki | Nathan D Lawson | Jaime A Rivera-Pérez | Erik J Sontheimer | Jonathan K Watts | Craig C Mello
eLife | 2021

Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as a therapeutic approach to correct mutations that cause disease. In its most precise form, genome editing can use cellular homology-directed repair (HDR) pathways to insert information from an exogenously supplied DNA-repair template (donor) directly into a targeted genomic location. Unfortunately, particularly for long insertions, toxicity and delivery considerations associated with repair template DNA can limit HDR efficacy. Here, we explore chemical modifications to both double-stranded and single-stranded DNA-repair templates. We describe 5'-terminal modifications, including in its simplest form the incorporation of triethylene glycol (TEG) moieties, that consistently increase the frequency of precision editing in the germlines of three animal models (Caenorhabditis elegans, zebrafish, mice) and in cultured human cells.

Pubmed ID: 34665130

Associated grants

  • Agency: NCATS NIH HHS, United States
    Id: UH3 TR002668
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM058800
  • Agency: NHLBI NIH HHS, United States
    Id: R35 HL140017
  • Agency: NCATS NIH HHS, United States
    Id: UG3 TR002668
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIH HHS, United States
    Id: R21 OD030004

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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ATCC (tool)

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Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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