Evidence map›Paper›PMID 30133337›Full record

ArticleNucleic acid therapeutics2018

Development of Locked Nucleic Acid Antisense Oligonucleotides Targeting Ebola Viral Proteins and Host Factor Niemann-Pick C1.

Jessica Chery, Andreas Petri, Alexandre Wagschal, Sun-Young Lim, James Cunningham, Shobha Vasudevan, Sakari Kauppinen, Anders M Näär

Open access · greenAbstract read
In one paragraph

Article in Nucleic acid therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Clinical applications of gene therapy for rare diseases: A review.International journal of experimental pathology · 2023
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  14. Synthesis and properties of oligonucleotides modified with anBeilstein journal of organic chemistry · 2021
    Article
  15. Article
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 3 institutions in 1 country.

Jessica Chery1 Massachusetts General Hospital Cancer Center , Charlestown, Massachusetts.
Andreas Petri3 Department of Clinical Medicine, Center for RNA Medicine, Aalborg University , Aalborg, Denmark .
Alexandre Wagschal1 Massachusetts General Hospital Cancer Center , Charlestown, Massachusetts.
Sun-Young Lim4 Department of Medicine, Brigham and Women's Hospital , Boston, Massachusetts.
James Cunningham4 Department of Medicine, Brigham and Women's Hospital , Boston, Massachusetts.
Shobha Vasudevan1 Massachusetts General Hospital Cancer Center , Charlestown, Massachusetts.
Sakari Kauppinen3 Department of Clinical Medicine, Center for RNA Medicine, Aalborg University , Aalborg, Denmark .
Anders M Näär1 Massachusetts General Hospital Cancer Center , Charlestown, Massachusetts.
Harvard University · USBrigham and Women's Hospital · USMassachusetts General Hospital · US

Funding

(PQC6) Molecular Determinants of Quiescent Cancer CellsR01CA185086 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI VASUDEVAN, SHOBHA · 2014 to 2017
$1.8M
Post-transcriptional Gene Expression of the TNF alpha by an FXR1a-associated microRNPR01GM100202 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI VASUDEVAN, SHOBHA · 2015 to 2019
$1.7M
NCI NIH HHS R01 CA185086NIGMS NIH HHS R01 GM100202
6 · The paper itself

Abstract

The Ebola virus is a zoonotic pathogen that can cause severe hemorrhagic fever in humans, with up to 90% lethality. The deadly 2014 Ebola outbreak quickly made an unprecedented impact on human lives. While several vaccines and therapeutics are under development, current approaches contain several limitations, such as virus mutational escape, need for formulation or refrigeration, poor scalability, long lead-time, and high cost. To address these challenges, we developed locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) to target critical Ebola viral proteins and the human intracellular host protein Niemann-Pick C1 (NPC1), required for viral entry into infected cells. We generated noninfectious viral luciferase reporter assays to identify LNA ASOs that inhibit translation of Ebola viral proteins in vitro and in human cells. We demonstrated specific inhibition of key Ebola genes VP24 and nucleoprotein, which inhibit a proper immune response and promote Ebola virus replication, respectively. We also identified LNA ASOs targeting human host factor NPC1 and demonstrated reduced infection by chimeric vesicular stomatitis virus harboring the Ebola glycoprotein, which directly binds to NPC1 for viral infection. These results support further in vivo testing of LNA ASOs in infectious Ebola virus disease animal models as potential therapeutic modalities for treatment of Ebola.

Indexed as

AnimalsDisease Models, AnimalEbolavirusHemorrhagic Fever, EbolaHumansImmunity, InnateMiceNiemann-Pick C1 ProteinNucleoproteinsOligonucleotidesOligonucleotides, AntisensePrimatesViral ProteinsVirus Replicationlocked nucleic acidNiemann-Pick C1 ProteinNucleoproteinsOligonucleotidesOligonucleotides, AntisenseViral ProteinsVP24 protein, Ebola virusantisense oligonucleotidesEbolaEbola virus (EBOV)locked nucleic acidsNiemann-Pick C1 (NPC1)

Identifiers

PMID30133337
PMCPMC6425983
OpenAlexW2888145792

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.