Evidence map›Paper›PMID 31341104›Full record

ArticleJCI insight2019

An effective cell-penetrating antibody delivery platform.

Andreas Herrmann, Toshikage Nagao, Chunyan Zhang, Christoph Lahtz, Yi-Jia Li, Chanyu Yue, Ronja Mülfarth, Hua Yu

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. A platform to deliver single and bi-specific Cas9/guide RNA to perturb genes in vitro and in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  4. Review
  5. Article
  6. Molecular and therapeutic advancements in Capicua (Frontiers in cell and developmental biology · 2024
    Review
  7. Review
  8. Post-genomic platform for development of oligonucleotide vaccines against RNA viruses: diamond cuts diamond.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Overcoming Physiological Barriers to Nanoparticle Delivery-Are We There Yet?Frontiers in bioengineering and biotechnology · 2019
    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

8 authors at 2 institutions in 1 country.

Andreas HerrmannDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Toshikage NagaoDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Chunyan ZhangDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Christoph LahtzDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Yi-Jia LiDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Chanyu YueDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Ronja MülfarthDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Hua YuDepartment of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, California, USA.
City of Hope · USSorrento Therapeutics (United States) · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Role of Stat3 in Tumor Immune Evasion and Immune SuppressionR01CA122976 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, HUA E · 2006 to 2015
$2.9M
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA122976
6 · The paper itself

Abstract

Despite their well-recognized success in the clinic, antibodies generally do not penetrate cellular membranes to target intracellular molecules, many of which underlie incurable diseases. Here we show that covalently conjugating phosphorothioated DNA oligonucleotides to antibodies enabled their efficient cellular internalization. Antibody cell penetration was partially mediated by membrane potential alteration. Moreover, without an antigen to bind, intracellular levels of the modified antibodies underwent cellular clearance, which involved efflux and lysosomal degradation, enabling detection of intended intracellular molecules as tested in fibroblasts, tumor cells, and T cells. This target-dependent cellular retention of modified antibodies extended to in vivo studies. Both local and systemic administrations of low doses of modified antibodies effectively inhibited intracellular targets, such as transcription factors Myc, interferon regulatory factor 4, and tyrosine-protein kinase SRC, and expression of their downstream genes in tumors, resulting in tumor cell apoptosis and tumor growth inhibition. This simple modification enables the use of antibodies to detect and modulate intracellular molecules in both cultured living cells and in whole animals, forming the foundation for a new paradigm for antibody-based research, diagnostics, and therapeutics.

Indexed as

AnimalsAntibodies, MonoclonalCell Line, TumorCell Membrane PermeabilityDrug Delivery SystemsHumansImmunoconjugatesMelanomaMiceOligodeoxyribonucleotidesXenograft Model Antitumor AssaysAntibodies, MonoclonalImmunoconjugatesOligodeoxyribonucleotidesImmunotherapyOncologyTherapeutics

Identifiers

PMID31341104
PMCPMC6675557
OpenAlexW2963495007

What OpenQuestion holds

Textmetadata
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.