Evidence map›Paper›PMID 30837588›Full record

ArticleScientific reports2019

Application of Locked Nucleic Acid Oligonucleotides for siRNA Preclinical Bioanalytics.

Mai B Thayer, Julie M Lade, David Doherty, Fang Xie, Babak Basiri, Omar S Barnaby, Noor S Bala, Brooke M Rock

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 13% 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, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Mai B ThayerAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA. mthayer@amgen.com.
Julie M LadeAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA.
David DohertyAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA.
Fang XieAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA.
Babak BasiriAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA.
Omar S BarnabyAmgen Research, Pharmacokinetics and Drug Metabolism, Thousand Oaks, 91320, USA.
Noor S BalaAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA.
Brooke M RockAmgen Research, Pharmacokinetics and Drug Metabolism, South San Francisco, 94080, USA. brooke@amgen.com.
Amgen (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the exquisite potential of siRNA as a therapeutic, the mechanism(s) responsible for the robust indirect exposure-response relationships have not been fully elucidated. To understand the siRNA properties linked to potent activity, requires the disposition of siRNA to be characterized. A technical challenge in the characterization is the detection and quantitation of siRNA from biological samples. Described herein, a Locked Nucleic Acid (LNA) Hybridization-Ligation ECL ELISA was designed for ultra-sensitive quantification of both sense and antisense strands of siRNA independent of structural modifica-tions. This assay was applied to measure siRNA in serum and tissue homogenate in preclinical species. We observed rapid clearance of siRNA from the systemic circulation which contrasted the prolonged accumulation within the tissue. The assay was also able to distinguish and quantify free siRNA from RNA-induced silencing complex (RISC) and Argonaute 2 (Ago2) associated with therapeutic siRNA. We utilized an orthogonal method, LC-MS, to investigate 3' exonuclease activity toward the antisense strand metabolism. Taken together, we have demonstrated that the LNA Hybridization-Ligation ECL ELISA is arobust analytical method with direct application to measuring the exposure of siRNA therapeutics seamlessly across biological matrices.

Indexed as

AnimalsEnzyme-Linked Immunosorbent AssayIntracellular SpaceNucleic Acid HybridizationOligonucleotidesOligonucleotides, AntisenseRNA, Small Interferinglocked nucleic acidOligonucleotidesOligonucleotides, AntisenseRNA, Small Interfering

Identifiers

PMID30837588
PMCPMC6401054
OpenAlexW2919875302

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.