Evidence map›Paper›PMID 38302906›Full record

ArticleBMC biology2024

Donor template delivery by recombinant adeno-associated virus for the production of knock-in mice.

Graham Duddy, Katherine Courtis, Juliette Horwood, Jessica Olsen, Helen Horsler, Tina Hodgson, Sunita Varsani-Brown, Abdullah Abdullah, Laura Denti, Hollie Lane and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Genome engineering with Cas9 and AAV repair templates, successes and pitfalls.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Graham DuddyThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Katherine CourtisThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Juliette HorwoodThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Jessica OlsenThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Helen HorslerThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Tina HodgsonThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Sunita Varsani-BrownThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Abdullah AbdullahThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Laura DentiThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Hollie LaneThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Fabio DelaquaThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Julia JanzenTransnetyx Inc, 8110 Cordova Rd. Suite 119, Cordova, TN, 38016, USA.
Molly StromThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Ian RosewellThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Katharine CrawleyThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Benjamin DaviesThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK. ben.davies@crick.ac.uk.ORCID 0000-0003-3623-600X
The Francis Crick Institute · GB

Funding

Cancer Research UK CC0199Medical Research Council CC0199Wellcome Trust CC0199
6 · The paper itself

Abstract

backgroundThe ability of recombinant adeno-associated virus to transduce preimplantation mouse embryos has led to the use of this delivery method for the production of genetically altered knock-in mice via CRISPR-Cas9. The potential exists for this method to simplify the production and extend the types of alleles that can be generated directly in the zygote, obviating the need for manipulations of the mouse genome via the embryonic stem cell route.

resultsWe present the production data from a total of 13 genetically altered knock-in mouse models generated using CRISPR-Cas9 electroporation of zygotes and delivery of donor repair templates via transduction with recombinant adeno-associated virus. We explore the efficiency of gene targeting at a total of 12 independent genetic loci and explore the effects of allele complexity and introduce strategies for efficient identification of founder animals. In addition, we investigate the reliability of germline transmission of the engineered allele from founder mice generated using this methodology. By comparing our production data against genetically altered knock-in mice generated via gene targeting in embryonic stem cells and their microinjection into blastocysts, we assess the animal cost of the two methods.

conclusionsOur results confirm that recombinant adeno-associated virus transduction of zygotes provides a robust and effective delivery route for donor templates for the production of knock-in mice, across a range of insertion sizes (0.9-4.7 kb). We find that the animal cost of this method is considerably less than generating knock-in models via embryonic stem cells and thus constitutes a considerable 3Rs reduction.

Indexed as

CRISPR-Cas SystemsDependovirusAnimalsGene Knock-In TechniquesGene TargetingMiceReproducibility of ResultsZygoteAdeno-associated virusCRISPR-Cas9ElectroporationGene editingKnock-in mouseZygote

Identifiers

PMID38302906
PMCPMC10836013
OpenAlexW4392785481

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.