Evidence map›Paper›PMID 17264131›Full record

ArticleNucleic acids research2007

Inhibition of MDR1 expression with altritol-modified siRNAs.

Michael Fisher, Mikhail Abramov, Arthur Van Aerschot, Dong Xu, Rudolph L Juliano, Piet Herdewijn

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 80 citations in OpenAlex.

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  9. Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier - from Targeting to Safe Administration.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017
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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 2 countries.

Michael FisherDepartment of Pharmacology, School of Medicine, University of North Carolina Chapel Hill NC 27599, USA.
Mikhail Abramov
Arthur Van Aerschot
Dong Xu
Rudolph L Juliano
Piet Herdewijn
Rega Institute for Medical Research · BEUniversity of North Carolina at Chapel Hill · US

Funding

TRANSPORT AND DELIVERY OF ANTISNESE OLIGONUCLEOTIDESP01GM059299 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JULIANO, RUDOLPH · 2000 to 2010
$11.7M
NIGMS NIH HHS P01 GM059299NIGMS NIH HHS P01 GM59299
6 · The paper itself

Abstract

Altritol-modified nucleic acids (ANAs) support RNA-like A-form structures when included in oligonucleotide duplexes. Thus altritol residues seem suitable as candidates for the chemical modification of siRNAs. Here we report that ANA-modified siRNAs targeting the MDR1 gene can exhibit improved efficacy as compared to unmodified controls. This was particularly true of ANA modifications at or near the 3' end of the sense or antisense strands, while modification at the 5' end of the antisense strand resulted in complete loss of activity. Multiple ANA modifications within the sense strand were also well tolerated. Duplexes with ANA modifications at appropriate positions in both strands were generally more effective than duplexes with one modified and one unmodified strand. Initial evidence suggests that the loss of activity associated with ANA modification of the 5'-antisense strand may be due to reduced phosphorylation at this site by cellular kinases. Treatment of drug resistant cells with MDR1-targeted siRNAs resulted in reduction of P-glycoprotein (Pgp) expression, parallel reduction in MDR1 message levels, increased accumulation of the Pgp substrate rhodamine 123, and reduced resistance to anti-tumor drugs. Interestingly, the duration of action of some of the ANA-modified siRNAs was substantially greater than that of unmodified controls. These observations suggest that altritol modifications may be helpful in developing siRNAs with enhanced pharmacological effectiveness.

Indexed as

RNA InterferenceAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Dose-Response Relationship, DrugMiceNIH 3T3 CellsPhosphorylationPolymerase Chain ReactionRhodamine 123RNA, MessengerRNA, Small InterferingSugar AlcoholsaltritolATP Binding Cassette Transporter, Subfamily B, Member 1Rhodamine 123RNA, MessengerRNA, Small InterferingSugar Alcohols

Identifiers

PMID17264131
PMCPMC1851637
OpenAlexW2122632025

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.