Evidence map›Paper›PMID 20530528›Full record

ArticleNucleic acids research2010

Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology.

Salvatore J Orlando, Yolanda Santiago, Russell C DeKelver, Yevgeniy Freyvert, Elizabeth A Boydston, Erica A Moehle, Vivian M Choi, Sunita M Gopalan, Jacqueline F Lou, James Li and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

95 citing papers in PubMed, 192 citations in OpenAlex.

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  19. Plant DNA Repair Pathways and Their Applications in Genome Engineering.Methods in molecular biology (Clifton, N.J.) · 2019
    Review
  20. Article

35 more citing papers are in PubMed but not listed here.

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

15 authors at 1 institution in 1 country.

Salvatore J OrlandoSangamo BioSciences, 501 Canal Bvld, Richmond, CA 94804, USA.
Yolanda Santiago
Russell C DeKelver
Yevgeniy Freyvert
Elizabeth A Boydston
Erica A Moehle
Vivian M Choi
Sunita M Gopalan
Jacqueline F Lou
James Li
Jeffrey C Miller
Michael C Holmes
Philip D Gregory
Fyodor D Urnov
Gregory J Cost
Sangamo BioSciences (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We previously demonstrated high-frequency, targeted DNA addition mediated by the homology-directed DNA repair pathway. This method uses a zinc-finger nuclease (ZFN) to create a site-specific double-strand break (DSB) that facilitates copying of genetic information into the chromosome from an exogenous donor molecule. Such donors typically contain two approximately 750 bp regions of chromosomal sequence required for homology-directed DNA repair. Here, we demonstrate that easily-generated linear donors with extremely short (50 bp) homology regions drive transgene integration into 5-10% of chromosomes. Moreover, we measure the overhangs produced by ZFN cleavage and find that oligonucleotide donors with single-stranded 5' overhangs complementary to those made by ZFNs are efficiently ligated in vivo to the DSB. Greater than 10% of all chromosomes directly incorporate this exogenous DNA via a process that is dependent upon and guided by complementary 5' overhangs on the donor DNA. Finally, we extend this non-homologous end-joining (NHEJ)-based technique by directly inserting donor DNA comprising recombinase sites into large deletions created by the simultaneous action of two separate ZFN pairs. Up to 50% of deletions contained a donor insertion. Targeted DNA addition via NHEJ complements our homology-directed targeted integration approaches, adding versatility to the manipulation of mammalian genomes.

Indexed as

Zinc FingersAnimalsCHO CellsChromosomes, MammalianCricetinaeCricetulusDeoxyribonucleases, Type II Site-SpecificDNADNA Breaks, Double-StrandedGene TargetingGenomeHumansK562 CellsSequence Homology, Nucleic AcidDeoxyribonucleases, Type II Site-SpecificDNAendodeoxyribonuclease FokI

Identifiers

PMID20530528
PMCPMC2926620
OpenAlexW2009043217

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.