Evidence map›Paper›PMID 36841822›Full record

ArticleNature communications2023

Single-cell quantification and dose-response of cytosolic siRNA delivery.

Hampus Hedlund, Hampus Du Rietz, Johanna M Johansson, Hanna C Eriksson, Wahed Zedan, Linfeng Huang, Jonas Wallin, Anders Wittrup

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 31 citations in OpenAlex.

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  20. Delivery Strategies of siRNA Therapeutics for Hair Loss Therapy.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

8 authors at 3 institutions in 2 countries.

Hampus HedlundDepartment of Clinical Sciences Lund, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.ORCID 0000-0002-3168-7920
Hampus Du RietzDepartment of Clinical Sciences Lund, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.ORCID 0000-0002-5530-3821
Johanna M JohanssonDepartment of Clinical Sciences Lund, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.ORCID 0000-0002-5090-9701
Hanna C ErikssonDepartment of Clinical Sciences Lund, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.ORCID 0000-0002-6652-7177
Wahed ZedanDepartment of Clinical Sciences Lund, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.
Linfeng HuangWang-Cai Biochemistry Lab, Division of Natural and Applied Sciences, Duke Kunshan University, Kunshan, Jiangsu, China.ORCID 0000-0002-0322-4929
Jonas WallinDepartment of Mathematical Statistics, Lund University, Lund, Sweden.ORCID 0000-0003-0381-6593
Anders WittrupDepartment of Clinical Sciences Lund, Oncology, Faculty of Medicine, Lund University, Lund, Sweden. anders.wittrup@med.lu.se.ORCID 0000-0003-4918-0500
Lund University · SEDuke Kunshan University · CNStatistics Sweden · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endosomal escape and subsequent cytosolic delivery of small interfering RNA (siRNA) therapeutics is believed to be highly inefficient. Since it has not been possible to quantify cytosolic amounts of delivered siRNA at therapeutic doses, determining delivery bottlenecks and total efficiency has been difficult. Here, we present a confocal microscopy-based method to quantify cytosolic delivery of fluorescently labeled siRNA during lipid-mediated delivery. This method enables detection and quantification of sub-nanomolar cytosolic siRNA release amounts from individual release events with measures of quantitation confidence for each event. Single-cell kinetics of siRNA-mediated knockdown in cells expressing destabilized eGFP unveiled a dose-response relationship with respect to knockdown induction, depth and duration in the range from several hundred to thousands of cytosolic siRNA molecules. Accurate quantification of cytosolic siRNA, and the establishment of the intracellular dose-response relationships, will aid the development and characterization of novel delivery strategies for nucleic acid therapeutics.

Indexed as

EndosomesCytosolRNA, Small InterferingRNA, Small Interfering

Identifiers

PMID36841822
PMCPMC9968291
OpenAlexW4322008833

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.