Evidence map›Paper›PMID 29937418›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018

Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles.

Reka Agnes Haraszti, Rachael Miller, Marie-Cecile Didiot, Annabelle Biscans, Julia F Alterman, Matthew R Hassler, Loic Roux, Dimas Echeverria, Ellen Sapp, Marian DiFiglia and 2 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.4field-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

58 citing papers in PubMed, 101 citations in OpenAlex.

  1. Review
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  4. Current trends in exosomes as therapeutic drug delivery systems.Naunyn-Schmiedeberg's archives of pharmacology · 2026
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  16. Basic Guide for Approaching Drug Delivery with Extracellular Vesicles.International journal of molecular sciences · 2024
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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

12 authors at 2 institutions in 1 country.

Reka Agnes HarasztiRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Rachael MillerRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Marie-Cecile DidiotRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Annabelle BiscansRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Julia F AltermanRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Matthew R HasslerRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Loic RouxRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Dimas EcheverriaRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Ellen SappMass General Institute for Neurodegenerative Disease, Boston, MA, USA.
Marian DiFigliaMass General Institute for Neurodegenerative Disease, Boston, MA, USA.
Neil AroninRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: neil.aronin@umassmed.edu.
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: anastasia.khvorova@umassmed.edu.
University of Massachusetts Chan Medical School · USMassachusetts General Hospital · US

Funding

University of Massachusetts Center for Clinical and Translational ScienceUL1TR000161 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUZURIAGA, KATHERINE F · 2012 to 2015
$11.0M
Expanding the chemical diversity of therapeutic oligonucleotides to treat neurodegenerative disordersR01NS104022 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2017 to 2026
$6.0M
Exosome based therapeutics in Huntington's diseaseUH3TR000888 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL, KHVOROVA, ANASTASIA · 2015 to 2017
$3.0M
Exosome based therapeutics in Huntington's diseaseUH2TR000888 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL · 2013 to 2014
$1.1M
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
NCATS NIH HHS UH2 TR000888NCATS NIH HHS UH3 TR000888NCATS NIH HHS UL1 TR000161NIH HHS S10 OD020012NINDS NIH HHS R01 NS104022
6 · The paper itself

Abstract

Extracellular vesicles are promising delivery vesicles for therapeutic RNAs. Small interfering RNA (siRNA) conjugation to cholesterol enables efficient and reproducible loading of extracellular vesicles with the therapeutic cargo. siRNAs are typically chemically modified to fit an application. However, siRNA chemical modification pattern has not been specifically optimized for extracellular vesicle-mediated delivery. Here we used cholesterol-conjugated, hydrophobically modified asymmetric siRNAs (hsiRNAs) to evaluate the effect of backbone, 5'-phosphate, and linker chemical modifications on productive hsiRNA loading onto extracellular vesicles. hsiRNAs with a combination of 5'-(E)-vinylphosphonate and alternating 2'-fluoro and 2'-O-methyl backbone modifications outperformed previously used partially modified siRNAs in extracellular vesicle-mediated Huntingtin silencing in neurons. Between two commercially available linkers (triethyl glycol [TEG] and 2-aminobutyl-1-3-propanediol [C7]) widely used to attach cholesterol to siRNAs, TEG is preferred compared to C7 for productive exosomal loading. Destabilization of the linker completely abolished silencing activity of loaded extracellular vesicles. The loading of cholesterol-conjugated siRNAs was saturated at ∼3,000 siRNA copies per extracellular vesicle. Overloading impaired the silencing activity of extracellular vesicles. The data reported here provide an optimization scheme for the successful use of hydrophobic modification as a strategy for productive loading of RNA cargo onto extracellular vesicles.

Indexed as

AnimalsCells, CulturedCholesterolExtracellular VesiclesHumansHuntingtin ProteinMiceMutationPropylene GlycolsRNA, Small InterferingCholesterolHTT protein, humanHuntingtin ProteinPropylene GlycolsRNA, Small Interferingchemical modificationexosomesextracellular vesiclesnanovesiclesoligonucleotidesRNA therapysiRNA

Identifiers

PMID29937418
PMCPMC6094392
OpenAlexW2809145613

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.