Evidence map›Paper›PMID 24465685›Full record

ArticlePloS one2014

Cell-penetrating peptide-mediated delivery of TALEN proteins via bioconjugation for genome engineering.

Jia Liu, Thomas Gaj, James T Patterson, Shannon J Sirk, Carlos F Barbas

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
12.7field-weighted citation impact, top 1% 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

69 citing papers in PubMed, 149 citations in OpenAlex.

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  14. Strategies for High-Efficiency Mutation Using the CRISPR/Cas System.Frontiers in cell and developmental biology · 2021
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9 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

5 authors at 1 institution in 1 country.

Jia LiuThe Departments of Chemistry and Cell and Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Thomas GajThe Departments of Chemistry and Cell and Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.
James T PattersonThe Departments of Chemistry and Cell and Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Shannon J SirkThe Departments of Chemistry and Cell and Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Carlos F BarbasThe Departments of Chemistry and Cell and Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Scripps Research Institute · US

Funding

Chemically Programmed ImmunityDP1CA174426 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI DAWSON, PHILIP E · 2012 to 2014
$2.3M
NCI NIH HHS DP1 CA174426NCI NIH HHS DP1CA174426
6 · The paper itself

Abstract

Transcription activator-like (TAL) effector nucleases (TALENs) have enabled the introduction of targeted genetic alterations into a broad range of cell lines and organisms. These customizable nucleases are comprised of programmable sequence-specific DNA-binding modules derived from TAL effector proteins fused to the non-specific FokI cleavage domain. Delivery of these nucleases into cells has proven challenging as the large size and highly repetitive nature of the TAL effector DNA-binding domain precludes their incorporation into many types of viral vectors. Furthermore, viral and non-viral gene delivery methods carry the risk of insertional mutagenesis and have been shown to increase the off-target activity of site-specific nucleases. We previously demonstrated that direct delivery of zinc-finger nuclease proteins enables highly efficient gene knockout in a variety of mammalian cell types with reduced off-target effects. Here we show that conjugation of cell-penetrating poly-Arg peptides to a surface-exposed Cys residue present on each TAL effector repeat imparted cell-penetrating activity to purified TALEN proteins. These modifications are reversible under reducing conditions and enabled TALEN-mediated gene knockout of the human CCR5 and BMPR1A genes at rates comparable to those achieved with transient transfection of TALEN expression vectors. These findings demonstrate that direct protein delivery, facilitated by conjugation of chemical functionalities onto the TALEN protein surface, is a promising alternative to current non-viral and viral-based methods for TALEN delivery into mammalian cells.

Indexed as

Cell-Penetrating PeptidesCell ProliferationEndonucleasesGene TargetingGenetic EngineeringHEK293 CellsHeLa CellsHumansMutagenesis, Site-DirectedReceptors, CCR5CCR5 protein, humanCell-Penetrating PeptidesEndonucleasesReceptors, CCR5

Identifiers

PMID24465685
PMCPMC3896395
OpenAlexW1993510145

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.