Evidence map›Paper›PMID 27585903›Full record

ArticlePharmaceutical research2016

Endocytic Transport of Polyplex and Lipoplex siRNA Vectors in HeLa Cells.

Mihael Lazebnik, Rahul K Keswani, Daniel W Pack

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  5. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
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  7. Article
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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

3 authors at 3 institutions in 1 country.

Mihael LazebnikDepartment of Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, Urbana, Illinois, USA.
Rahul K KeswaniDepartment of Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, Urbana, Illinois, USA.
Daniel W PackDepartment of Chemical & Materials Engineering, University of Kentucky, Lexington, Kentucky, USA. dan.pack@uky.edu.
University of Illinois Urbana-Champaign · USUniversity of Kentucky · USUniversity of Michigan–Ann Arbor · US

Funding

Effects of Uptake Mechanism on Polyplex Design CriteriaR01GM085222 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI PACK, DANIEL W · 2009 to 2012
$1.2M
NIGMS NIH HHS R01 GM085222
6 · The paper itself

Abstract

purposesiRNA may be delivered as electrostatic complexes with cationic lipids (lipoplexes) or polycations (polyplexes). The purpose of this project was to determine the effect of cellular internalization mechanism(s) on siRNA-mediated gene silencing efficiency.

methodsLipoplexes were formed comprising siRNA and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), cholesterol and dioleoyl phosphatidylethanolamine (DOPE), and polyplexes comprised siRNA with polyethylenimine (PEI). During transfections, specific uptake mechanisms were inhibited by pharmacological agents and RNAi-mediated knockdown of proteins involved in various endocytosis pathways. Confocal fluorescence microscopy further elucidated the predominant endocytic pathways of siRNA delivery via colocalization of vectors with endocytic vesicle markers.

resultsInhibition of macropinocytosis (MP), caveolin-mediated endocytosis (CvME), flotillin-mediated endocytosis (FME) and knockdown of ARF6 significantly decreased PEI/siRNA-mediated gene silencing. Inhibition of endocytosis pathways, however, had negligible effect on lipoplex uptake and gene silencing mediated by lipoplexes. Rather, internalization of lipoplexes and subsequent siRNA-mediated gene silencing occurred via an energy-independent process.

conclusionsMP, CvME and FME, but not the acidified clathrin-mediated pathway, lead to effective gene silencing by PEI/siRNA polyplexes. Lipoplexes, in contrast, deliver siRNA primarily by direct fusion of the liposomal and cellular membranes. These results provide a new understanding of the mechanisms of siRNA delivery materials in HeLa cells and may aid in design of more effective RNAi strategies.

Indexed as

Cell Culture TechniquesCell SurvivalCholesterolDrug Delivery SystemsDrug LiberationEndocytosisFatty Acids, MonounsaturatedGene SilencingHeLa CellsHumansLiposomesPhosphatidylethanolaminesPolyethyleneimineQuaternary Ammonium CompoundsRNA, Small Interfering1,2-dielaidoylphosphatidylethanolamine1,2-dioleoyloxy-3-(trimethylammonium)propaneCholesteroldioleoyl phosphatidylethanolamineFatty Acids, MonounsaturatedLiposomesPhosphatidylethanolaminesPolyethyleneimineQuaternary Ammonium CompoundsRNA, Small InterferingendocytosisliposomespolyethyleniminesiRNA delivery

Identifiers

PMID27585903
OpenAlexW2507219810

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.