Evidence map›Paper›PMID 21345934›Full record

ArticleNucleic acids research2011

Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes.

Erich Koller, Thomas M Vincent, Alfred Chappell, Soma De, Muthiah Manoharan, C Frank Bennett

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.

0numbers the graph read from it
0cells of the map it votes in
163citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

163 citing papers in PubMed, 277 citations in OpenAlex.

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  6. LncRNA Knockdown Using Gapmer Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2026
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  10. Widespread tissue delivery of antagomiRs via intramuscular administration.Molecular therapy. Methods & clinical development · 2025
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  20. Review

103 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

6 authors at 2 institutions in 1 country.

Erich KollerIsis Pharmaceuticals Inc., 1896 Rutherford Road, Carlsbad, CA 92008 and Alnylam Pharmaceuticals Inc., 300 Third Street, Cambridge, MA 02142, USA. ekoller@isisph.com
Thomas M Vincent
Alfred Chappell
Soma De
Muthiah Manoharan
C Frank Bennett
Ionis Pharmaceuticals (United States) · USAlnylam Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Single-stranded antisense oligonucleotides (SSOs) are used to modulate the expression of genes in animal models and are being investigated as potential therapeutics. To better understand why synthetic SSOs accumulate in the same intracellular location as the target RNA, we have isolated a novel mouse hepatocellular SV40 large T-antigen carcinoma cell line, MHT that maintains the ability to efficiently take up SSOs over several years in culture. Sequence-specific antisense effects are demonstrated at low nanomolar concentrations. SSO accumulation into cells is both time and concentration dependent. At least two distinct cellular pathways are responsible for SSO accumulation in cells: a non-productive pathway resulting in accumulation in lysosomes, and a functional uptake pathway in which the SSO gains access to the targeted RNA. We demonstrate that functional uptake, as defined by a sequence-specific reduction in target mRNA, is inhibited by brefeldin A and chloroquine. Functional uptake is blocked by siRNA inhibitors of the adaptor protein AP2M1, but not by clathrin or caveolin. Furthermore, we document that treatment of mice with an AP2M1 siRNA blocks functional uptake into liver tissue. Functional uptake of SSO appears to be mediated by a novel clathrin- and caveolin-independent endocytotic process.

Indexed as

AnimalsCell Line, TumorEndocytosisHepatocytesKineticsMaleMiceMice, Inbred BALB CMice, TransgenicOligonucleotides, AntisensePhosphorothioate OligonucleotidesOligonucleotides, AntisensePhosphorothioate Oligonucleotides

Identifiers

PMID21345934
PMCPMC3113586
OpenAlexW2061092005

What OpenQuestion holds

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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.