Evidence map›Paper›PMID 25756962›Full record

ArticleMolecular therapy. Nucleic acids2015

Improved cell-penetrating zinc-finger nuclease proteins for precision genome engineering.

Jia Liu, Thomas Gaj, Mark C Wallen, Carlos F Barbas

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

Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Lysosomal storage diseases: current therapies and future alternatives.Journal of molecular medicine (Berlin, Germany) · 2020
    Review
  15. Article
  16. Article
  17. Non-Viral Delivery To Enable Genome Editing.Trends in biotechnology · 2019
    Review
  18. Review
  19. Article
  20. 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

4 authors at 2 institutions in 2 countries.

Jia Liu1] The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA [2] Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA [3] Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA [4] Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, China.
Thomas Gaj1] The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA [2] Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA [3] Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Mark C Wallen1] The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA [2] Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA [3] Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Carlos F Barbas1] The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA [2] Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA [3] Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA [4] Deceased.
Scripps Research Institute · USShanghaiTech University · CN

Funding

Genomic modification with purified nuclease proteins for HIV-1 therapyR01DE025167 · NIDCR · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2014 to 2018
$3.7M
Chemically Programmed ImmunityDP1CA174426 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI DAWSON, PHILIP E · 2012 to 2014
$2.3M
NCI NIH HHS DP1 CA174426NIDCR NIH HHS R01 DE025167
6 · The paper itself

Abstract

Safe, efficient, and broadly applicable methods for delivering site-specific nucleases into cells are needed in order for targeted genome editing to reach its full potential for basic research and medicine. We previously reported that zinc-finger nuclease (ZFN) proteins have the innate capacity to cross cell membranes and induce genome modification via their direct application to human cells. Here, we show that incorporation of tandem nuclear localization signal (NLS) repeats into the ZFN protein backbone enhances cell permeability nearly 13-fold and that single administration of multi-NLS ZFN proteins leads to genome modification rates of up to 26% in CD4(+) T cells and 17% in CD34(+) hematopoietic stem/progenitor cells. In addition, we show that multi-NLS ZFN proteins attenuate off-target effects and that codelivery of ZFN protein pairs facilitates dual gene modification frequencies of 20-30% in CD4(+) T cells. These results illustrate the applicability of ZFN protein delivery for precision genome engineering.

Identifiers

PMID25756962
PMCPMC4354341
OpenAlexW2017970337

What OpenQuestion holds

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Registered trials

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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.