Evidence map›Paper›PMID 31844114›Full record

ArticleScientific reports2019

A ligand-based system for receptor-specific delivery of proteins.

Mariano Maffei, Chiara Morelli, Ellie Graham, Stefano Patriarca, Laura Donzelli, Balint Doleschall, Fernanda de Castro Reis, Linda Nocchi, Cora H Chadick, Luc Reymond and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 19% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. 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

14 authors at 5 institutions in 4 countries.

Mariano MaffeiEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy. mariano.maffei@embl.it.
Chiara MorelliEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Ellie GrahamEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Stefano PatriarcaEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Laura DonzelliEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Balint DoleschallEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Fernanda de Castro ReisEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Linda NocchiEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Cora H ChadickEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Luc ReymondBiomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
Ivan R CorrêaNew England Biolabs, Ipswich, MA, 01938, USA.
Kai JohnssonDepartment of Chemical Biology, Max Plank Institute for Medical Research, 69120, Heidelberg, Germany.
Jamie A HackettEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy.
Paul A HeppenstallEuropean Molecular Biology Laboratory (EMBL) Rome, Adriano Buzzati-Traverso Campus, 00015, Monterotondo, Italy. paul.heppenstall@sissa.it.
European Molecular Biology Laboratory · ITÉcole Polytechnique Fédérale de Lausanne · CHHeidelberg University · DEMax Planck Institute for Medical Research · DENew England Biolabs (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand's cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases.

Indexed as

AnimalsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9CRISPR-Cas SystemsDependovirusGene EditingGenetic TherapyGene Transfer TechniquesKeratinocytesLigandsMiceMice, Inbred C57BLMice, TransgenicProteinsSkinCRISPR-Associated Protein 9LigandsProteins

Identifiers

PMID31844114
PMCPMC6915567
OpenAlexW2994731873

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.