Evidence map›Paper›PMID 38214218›Full record

ArticleMolecular pharmaceutics2024

A Modular Albumin-Oligonucleotide Biomolecular Assembly for Delivery of Antisense Therapeutics.

Marwa Elkhashab, Yeter Dilek, Morten Foss, Laura B Creemers, Kenneth A Howard

Open access · hybridAbstract read
In one paragraph

Article in Molecular pharmaceutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

5 authors at 2 institutions in 2 countries.

Marwa ElkhashabInterdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.ORCID 0000-0001-6386-7849
Yeter DilekDepartment of Orthopedics, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
Morten FossInterdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark.
Laura B CreemersDepartment of Orthopedics, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.ORCID 0000-0002-1585-3052
Kenneth A HowardInterdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.ORCID 0000-0002-9407-278X
Aarhus University · DKUniversity Medical Center Utrecht · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antisense nucleic acid drugs are susceptible to nuclease degradation, rapid renal clearance, and short circulatory half-life. In this work, we introduce a modular-based recombinant human albumin-oligonucleotide (rHA-cODN) biomolecular assembly that allows incorporation of a chemically stabilized therapeutic gapmer antisense oligonucleotide (ASO) and FcRn-driven endothelial cellular recycling. A phosphodiester ODN linker (cODN) was conjugated to recombinant human albumin (rHA) using maleimide chemistry, after which a complementary gapmer ASO, targeting ADAMTS5 involved in osteoarthritis pathogenesis, was annealed. The rHA-cODN/ASO biomolecular assembly production, fluorescence labeling, and purity were confirmed using polyacrylamide gel electrophoresis. ASO release was triggered by DNase-mediated degradation of the linker strand, reaching 40% in serum after 72 h, with complete release observed following 30 min of incubation with DNase. Cellular internalization and trafficking of the biomolecular assembly using confocal microscopy in C28/I2 cells showed higher uptake and endosomal localization by increasing incubation time from 4 to 24 h. FcRn-mediated cellular recycling of the assembly was demonstrated in FcRn-expressing human microvascular endothelial cells. ADAMTS5 in vitro silencing efficiency reached 40%, which was comparable to free gapmer after 72 h incubation with human osteoarthritis patients' chondrocytes. This work introduces a versatile biomolecular modular-based "Plug-and-Play" platform potentially applicable for albumin-mediated half-life extension for a range of different types of ODN therapeutics.

Indexed as

OligonucleotidesOsteoarthritisAlbuminsDeoxyribonucleasesEndothelial CellsHumansOligonucleotides, AntisenseSerum Albumin, HumanAlbuminsDeoxyribonucleasesOligonucleotidesOligonucleotides, AntisenseSerum Albumin, HumanADAMTS5albuminantisense oligonucleotidebiomolecular assembly, FcRnosteoarthritis

Identifiers

PMID38214218
PMCPMC10848253
OpenAlexW4390789377

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.