Evidence map›Paper›PMID 26351679›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Targeting protein translation, RNA splicing, and degradation by morpholino-based conjugates in Plasmodium falciparum.

Aprajita Garg, Donna Wesolowski, Dulce Alonso, Kirk W Deitsch, Choukri Ben Mamoun, Sidney Altman

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Nucleic-Acid Structures as Intracellular Probes for Live Cells.Advanced materials (Deerfield Beach, Fla.) · 2020
    Review
  7. Review
  8. Rocaglates as dual-targeting agents for experimental cerebral malaria.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  9. Article
  10. Antisense antimicrobial therapeutics.Current opinion in microbiology · 2016
    Review
  11. Potential ofIranian journal of parasitology
    Article
  12. 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

6 authors at 2 institutions in 1 country.

Aprajita GargDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
Donna WesolowskiDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520;
Dulce AlonsoDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520;
Kirk W DeitschDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065.
Choukri Ben MamounDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
Sidney AltmanDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520; sidney.altman@yale.edu.
Yale University · USCornell University · US

Funding

Var gene regulation and antigenic variation in malariaR01AI052390 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI DEITSCH, KIRK W · 2002 to 2019
$6.6M
Development of novel therapeutics for Babesia microti infectionR21AI109486 · NIAID · YALE UNIVERSITY · PI BEN MAMOUN, CHOUKRI · 2014 to 2015
$458k
NIAID NIH HHS AI109486NIAID NIH HHS AI116930NIAID NIH HHS R01 AI052390NIAID NIH HHS R21 AI109486
6 · The paper itself

Abstract

Identification and genetic validation of new targets from available genome sequences are critical steps toward the development of new potent and selective antimalarials. However, no methods are currently available for large-scale functional analysis of the Plasmodium falciparum genome. Here we present evidence for successful use of morpholino oligomers (MO) to mediate degradation of target mRNAs or to inhibit RNA splicing or translation of several genes of P. falciparum involved in chloroquine transport, apicoplast biogenesis, and phospholipid biosynthesis. Consistent with their role in the parasite life cycle, down-regulation of these essential genes resulted in inhibition of parasite development. We show that a MO conjugate that targets the chloroquine-resistant transporter PfCRT is effective against chloroquine-sensitive and -resistant parasites, causes enlarged digestive vacuoles, and renders chloroquine-resistant strains more sensitive to chloroquine. Similarly, we show that a MO conjugate that targets the PfDXR involved in apicoplast biogenesis inhibits parasite growth and that this defect can be rescued by addition of isopentenyl pyrophosphate. MO-based gene regulation is a viable alternative approach to functional analysis of the P. falciparum genome.

Indexed as

AnimalsAntimalarialsArtemisininsChloroquineDown-RegulationDrug ResistanceFlow CytometryGenes, ReporterHemiterpenesLuciferasesMorpholinosOrganophosphorus CompoundsParasitesPeptidesPlasmodium falciparumProtein BiosynthesisAntimalarialsartemisininArtemisininsChloroquineHemiterpenesisopentenyl pyrophosphateLuciferasesMorpholinosOrganophosphorus CompoundsPeptidesRNA, Messengergene expressionintraerythrocytic developmentmalariapeptide conjugated morpholino oligomervivo morpholino oligomer

Identifiers

PMID26351679
PMCPMC4586866
OpenAlexW2139254872

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.