Evidence map›Paper›PMID 21804077›Full record

ArticleThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society2011

Biodistribution of small interfering RNA at the organ and cellular levels after lipid nanoparticle-mediated delivery.

Bin Shi, Ed Keough, Andrea Matter, Karen Leander, Stephanie Young, Ed Carlini, Alan B Sachs, Weikang Tao, Marc Abrams, Bonnie Howell and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

66 citing papers in PubMed, 120 citations in OpenAlex.

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6 more citing papers are in PubMed but not listed here.

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

11 authors at 1 institution in 1 country.

Bin ShiDepartment of RNA Therapeutics, Merck Research Laboratories, Merck & Co, West Point, Pennsylvania 19486, USA. bin_shi@merck.com
Ed Keough
Andrea Matter
Karen Leander
Stephanie Young
Ed Carlini
Alan B Sachs
Weikang Tao
Marc Abrams
Bonnie Howell
Laura Sepp-Lorenzino
Merck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemically stabilized small interfering RNA (siRNA) can be delivered systemically by intravenous injection of lipid nanoparticles (LNPs) in rodents and primates. The biodistribution and kinetics of LNP-siRNA delivery in mice at organ and cellular resolution have been studied using immunofluorescence (IF) staining and quantitative polymerase chain reaction (qPCR). At 0.5 and 2 hr post tail vein injection of Cy5-labeled siRNA encapsulated in LNP, the organ rank-order of siRNA levels is liver > spleen > kidney, with only negligible accumulation in duodenum, lung, heart, and brain. Similar conclusions were drawn by using qPCR to measure tissue siRNA levels as a secondary end point. siRNA levels in these tissues decreased by more than 10-fold after 24 hr. Within the liver, LNPs delivered siRNA to hepatocytes, Kupffer cells, and sinusoids in a time-dependent manner, as revealed by IF staining and signal quantitation methods established using OPERA/Columbus software. siRNA first accumulated in liver sinusoids and trafficked to hepatocytes by 2 hr post dose, corresponding to the onset of target mRNA silencing. Fluorescence in situ hybridization methods were used to detect both strands of siRNA in fixed tissues. Collectively, the authors have implemented a platform to evaluate biodistribution of siRNA across cell types and across tissues in vivo, with the objective of elucidating the pharmacokinetic and pharmacodynamic relationship to guide optimization of delivery vehicles.

Indexed as

LipidsNanoparticlesAnimalsAutoantigensDrug CarriersFluorescent Antibody TechniqueGene Knockdown TechniquesIn Situ Hybridization, FluorescenceMiceRibonucleoproteinsRNA, MessengerRNA, Small InterferingSS-B AntigenTissue DistributionAutoantigensDrug CarriersLipidsRibonucleoproteinsRNA, MessengerRNA, Small InterferingSS-B Antigen

Identifiers

PMID21804077
PMCPMC3261601
OpenAlexW1988464677

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.