Evidence map›Paper›PMID 35733339›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022

Lipid nanoparticle-mediated silencing of osteogenic suppressor GNAS leads to osteogenic differentiation of mesenchymal stem cells in vivo.

Genc Basha, Andrew G Cottle, Thavaneetharajah Pretheeban, Karen Yt Chan, Dominik Witzigmann, Robert N Young, Fabio Mv Rossi, Pieter R Cullis

Open access · greenAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 21 citations in OpenAlex.

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  15. Bone Targeting Nanoparticles for the Treatment of Osteoporosis.International journal of nanomedicine · 2024
    Review
  16. Article
  17. Nano letters · 2023
    Article
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 2 institutions in 2 countries.

Genc BashaNanoMedicines Research Group, Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: gbasha@mail.ubc.ca.
Andrew G CottleNanoMedicines Research Group, Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Thavaneetharajah PretheebanSchool of Biomedical Engineering and Department of Medical Genetics, Biomedical Research Centre University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Karen Yt ChanNanoMedicines Research Group, Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Dominik WitzigmannNanoMedicines Research Group, Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; NanoMedicines Innovation Network (NMIN), University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Robert N YoungDepartment of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
Fabio Mv RossiSchool of Biomedical Engineering and Department of Medical Genetics, Biomedical Research Centre University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Pieter R CullisNanoMedicines Research Group, Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; NanoMedicines Innovation Network (NMIN), University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
University of British Columbia · CASimon Fraser University · CA

Funding

CIHR 122069
6 · The paper itself

Abstract

Approved drugs for the treatment of osteoporosis can prevent further bone loss but do not stimulate bone formation. Approaches that improve bone density in metabolic diseases are needed. Therapies that take advantage of the ability of mesenchymal stem cells (MSCs) to differentiate into various osteogenic lineages to treat bone disorders are of particular interest. Here we examine the ability of small interfering RNA (siRNA) to enhance osteoblast differentiation and bone formation by silencing the negative suppressor gene GNAS in bone MSCs. Using clinically validated lipid nanoparticle (LNP) siRNA delivery systems, we show that silencing the suppressor gene GNAS in vitro in MSCs leads to molecular and phenotypic changes similar to those seen in osteoblasts. Further, we demonstrate that these LNP-siRNAs can transfect a large proportion of mice MSCs in the compact bone following intravenous injection. Transfection of MSCs in various animal models led to silencing of GNAS and enhanced differentiation of MSCs into osteoblasts. These data demonstrate the potential for LNP delivery of siRNA to enhance the differentiation of MSCs into osteoblasts, and suggests that they are a promising approach for the treatment of osteoporosis and other bone diseases.

Indexed as

Mesenchymal Stem CellsOsteoporosisAnimalsCell DifferentiationCells, CulturedLiposomesMiceNanoparticlesOsteoblastsOsteogenesisRNA, Small InterferingLipid NanoparticlesLiposomesRNA, Small Interferingbone formationgene silencingGNASlipid nanoparticlesmesenchymal stem cellssiRNA

Identifiers

PMID35733339
PMCPMC9481989
OpenAlexW4283384326

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.