Evidence map›Paper›PMID 29432571›Full record

ArticleNucleic acids research2018

Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo.

Matthew R Hassler, Anton A Turanov, Julia F Alterman, Reka A Haraszti, Andrew H Coles, Maire F Osborn, Dimas Echeverria, Mehran Nikan, William E Salomon, Loïc Roux and 8 more

Abstract readComparative Study
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
–field-weighted citation impact
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

115 citing papers in PubMed.

  1. Review
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  7. Article
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  9. Article
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  11. Article
  12. Review
  13. Review
  14. Article
  15. Intravenous lipid-siRNA conjugate mediates gene silencing at the blood-brain barrier and blood-CSF barrier.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  20. Article

55 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

18 authors.

Matthew R HasslerRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Anton A TuranovRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Julia F AltermanRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Reka A HarasztiRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Andrew H ColesRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Maire F OsbornRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Dimas EcheverriaRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Mehran NikanRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
William E SalomonRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Loïc RouxRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Bruno M D C GodinhoRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Sarah M DavisRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
David V MorrisseyNovartis Institute of Biomedical Research, USA.
Phillip D ZamoreRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
S Ananth KarumanchiBeth Israel Deaconess Medical Center, Harvard Medical School, USA.
Melissa J MooreRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Neil AroninRNA Therapeutics Institute, University of Massachusetts Medical School, USA.
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Medical School, USA.

Funding

Development of RNAi based sFLT1-targeting therapeutics for treatment of PreeclampsiaR01HD086111 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2016 to 2020
$3.4M
Inter and intra-cellular trafficking pathways for natural and therapeutic RNAsR01GM108803 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2014 to 2018
$2.0M
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
NICHD NIH HHS R01 HD086111NIGMS NIH HHS R01 GM108803NIH HHS S10 OD020012
6 · The paper itself

Abstract

Small interfering RNA (siRNA)-based drugs require chemical modifications or formulation to promote stability, minimize innate immunity, and enable delivery to target tissues. Partially modified siRNAs (up to 70% of the nucleotides) provide significant stabilization in vitro and are commercially available; thus are commonly used to evaluate efficacy of bio-conjugates for in vivo delivery. In contrast, most clinically-advanced non-formulated compounds, using conjugation as a delivery strategy, are fully chemically modified (100% of nucleotides). Here, we compare partially and fully chemically modified siRNAs in conjugate mediated delivery. We show that fully modified siRNAs are retained at 100x greater levels in various tissues, independently of the nature of the conjugate or siRNA sequence, and support productive mRNA silencing. Thus, fully chemically stabilized siRNAs may provide a better platform to identify novel moieties (peptides, aptamers, small molecules) for targeted RNAi delivery.

Indexed as

RNA InterferenceRNA Processing, Post-TranscriptionalAnimalsAptamers, NucleotideCells, CulturedDrug Delivery SystemsFemaleGenetic VectorsHeLa CellsHumansLipidsMice, Inbred C57BLPeptidesRNA, Small InterferingTissue DistributionAptamers, NucleotideLipidsPeptidesRNA, Small Interfering

Identifiers

PMID29432571
PMCPMC5861422

What OpenQuestion holds

Textmetadata
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.