Evidence map›Paper›PMID 26738816›Full record

ArticleNature communications2016

Multi-reporter selection for the design of active and more specific zinc-finger nucleases for genome editing.

Benjamin L Oakes, Danny F Xia, Elizabeth F Rowland, Denise J Xu, Irina Ankoudinova, Jennifer S Borchardt, Lei Zhang, Patrick Li, Jeffrey C Miller, Edward J Rebar and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. A Chimeric ORF Fusion Phenotypic Reporter forJournal of fungi (Basel, Switzerland) · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Delivery technologies for genome editing.Nature reviews. Drug discovery · 2017
    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

11 authors at 3 institutions in 1 country.

Benjamin L OakesThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Danny F XiaSangamo BioSciences Inc., Richmond, California 94804, USA.
Elizabeth F RowlandThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Denise J XuThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Irina AnkoudinovaSangamo BioSciences Inc., Richmond, California 94804, USA.
Jennifer S BorchardtSangamo BioSciences Inc., Richmond, California 94804, USA.
Lei ZhangSangamo BioSciences Inc., Richmond, California 94804, USA.
Patrick LiSangamo BioSciences Inc., Richmond, California 94804, USA.
Jeffrey C MillerSangamo BioSciences Inc., Richmond, California 94804, USA.
Edward J RebarSangamo BioSciences Inc., Richmond, California 94804, USA.
Marcus B NoyesThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Sangamo BioSciences (United States) · USPrinceton University · USInstitute for Systems Biology · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Engineered nucleases have transformed biological research and offer great therapeutic potential by enabling the straightforward modification of desired genomic sequences. While many nuclease platforms have proven functional, all can produce unanticipated off-target lesions and have difficulty discriminating between homologous sequences, limiting their therapeutic application. Here we describe a multi-reporter selection system that allows the screening of large protein libraries to uncover variants able to discriminate between sequences with substantial homology. We have used this system to identify zinc-finger nucleases that exhibit high cleavage activity (up to 60% indels) at their targets within the CCR5 and HBB genes and strong discrimination against homologous sequences within CCR2 and HBD. An unbiased screen for off-target lesions using a novel set of CCR5-targeting nucleases confirms negligible CCR2 activity and demonstrates minimal off-target activity genome wide. This system offers a straightforward approach to generate nucleases that discriminate between similar targets and provide exceptional genome-wide specificity.

Indexed as

Zinc FingersAnimalsDeoxyribonucleasesDNA-Binding ProteinsGene Expression Regulation, EnzymologicGenes, ReporterGenomeHumansPeptide LibraryReceptors, CCR2Receptors, CCR5DeoxyribonucleasesDNA-Binding ProteinsPeptide LibraryReceptors, CCR2Receptors, CCR5

Identifiers

PMID26738816
PMCPMC4729830
OpenAlexW2265806354

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.