Evidence map›Paper›PMID 34879171›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2022

Chemically Synthesized, Self-Assembling Small Interfering RNA-Prohead RNA Molecules Trigger Dicer-Independent Gene Silencing.

Alyssa C Hill, Daniël van Leeuwen, Verena Schlösser, Alok Behera, Bogdan Mateescu, Jonathan Hall

Open access · hybridAbstract read
In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. 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 1 institution in 1 country.

Alyssa C HillETH Zürich, Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland.ORCID http://orcid.org/0000-0002-4767-5780
Daniël van LeeuwenETH Zürich, Department of Biology, Wolfgang-Pauli-Strasse 27, 8093, Zürich, Switzerland.
Verena SchlösserETH Zürich, Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland.ORCID http://orcid.org/0000-0001-5734-1234
Alok BeheraETH Zürich, Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland.
Bogdan MateescuETH Zürich, Department of Biology, Wolfgang-Pauli-Strasse 27, 8093, Zürich, Switzerland.ORCID http://orcid.org/0000-0002-0937-352X
Jonathan HallETH Zürich, Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland.ORCID http://orcid.org/0000-0003-4160-7135
ETH Zurich · CH

Funding

Novartis Research Foundation (Novartis Forschungsstiftung)
6 · The paper itself

Abstract

RNA interference (RNAi) mediated by small interfering RNA (siRNA) duplexes is a powerful therapeutic modality, but the translation of siRNAs from the bench into clinical application has been hampered by inefficient delivery in vivo. An innovative delivery strategy involves fusing siRNAs to a three-way junction (3WJ) motif derived from the phi29 bacteriophage prohead RNA (pRNA). Chimeric siRNA-3WJ molecules are presumed to enter the RNAi pathway through Dicer cleavage. Here, we fused siRNAs to the phi29 3WJ and two phylogenetically related 3WJs. We confirmed that the siRNA-3WJs are substrates for Dicer in vitro. However, our results reveal that siRNA-3WJs transfected into Dicer-deficient cell lines trigger potent gene silencing. Interestingly, siRNA-3WJs transfected into an Argonaute 2-deficient cell line also retain some gene silencing activity. siRNA-3WJs are most efficient when the antisense strand of the siRNA duplex is positioned 5' of the 3WJ (5'-siRNA-3WJ) relative to 3' of the 3WJ (3'-siRNA-3WJ). This work sheds light on the functional properties of siRNA-3WJs and offers a design rule for maximizing their potency in the human RNAi pathway.

Indexed as

Gene SilencingHumansRNA InterferenceRNA, Small InterferingRNA, Small Interferingpackaging RNAprohead RNARNA nanotechnologysmall interfering RNAthree-way junction

Identifiers

PMID34879171
PMCPMC9305526
OpenAlexW4200413262

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.