Evidence map›Paper›PMID 34285203›Full record

ArticleNature communications2021

Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers.

Chengxi Li, Alex J Callahan, Mark D Simon, Kyle A Totaro, Alexander J Mijalis, Kruttika-Suhas Phadke, Genwei Zhang, Nina Hartrampf, Carly K Schissel, Ming Zhou and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed, 56 citations in OpenAlex.

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  12. Machine Learning Guides Peptide Nucleic Acid Flow Synthesis and Sequence Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
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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

16 authors at 6 institutions in 2 countries.

Chengxi Li *Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Alex J Callahan *Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Mark D SimonDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kyle A TotaroDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Alexander J MijalisDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kruttika-Suhas PhadkeDepartment of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
Genwei ZhangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nina HartrampfDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0003-0875-6390
Carly K SchisselDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ming ZhouSarepta Therapeutics, Cambridge, MA, USA.
Hong ZongSarepta Therapeutics, Cambridge, MA, USA.
Gunnar J HansonSarepta Therapeutics, Cambridge, MA, USA.
Andrei LoasDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nicola L B PohlDepartment of Chemistry, Indiana University, Bloomington, IN, USA.ORCID 0000-0001-7747-8983
David E VerhoevenDepartment of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
Bradley L PenteluteDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. blp@mit.edu.ORCID 0000-0002-7242-801X
Massachusetts Institute of Technology · USSarepta Therapeutics (United States) · USIowa State University · USBroad Institute · USIndiana University Bloomington · USUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rapid development of antisense therapies can enable on-demand responses to new viral pathogens and make personalized medicine for genetic diseases practical. Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates to fill such a role, but their challenging synthesis limits their widespread application. To rapidly prototype potential PMO drug candidates, we report a fully automated flow-based oligonucleotide synthesizer. Our optimized synthesis platform reduces coupling times by up to 22-fold compared to previously reported methods. We demonstrate the power of our automated technology with the synthesis of milligram quantities of three candidate therapeutic PMO sequences for an unserved class of Duchenne muscular dystrophy (DMD). To further test our platform, we synthesize a PMO that targets the genomic mRNA of SARS-CoV-2 and demonstrate its antiviral effects. This platform could find broad application not only in designing new SARS-CoV-2 and DMD antisense therapeutics, but also for rapid development of PMO candidates to treat new and emerging diseases.

Indexed as

AnimalsChemistry, PharmaceuticalChemistry Techniques, SyntheticChlorocebus aethiopsCommunicable Diseases, EmergingCOVID-19COVID-19 Drug TreatmentDisease Models, AnimalHigh-Throughput Screening AssaysHumansMorpholinosMuscular Dystrophy, DuchenneOligonucleotides, AntisensePrecision MedicineRNA, MessengerRNA, ViralMorpholinosOligonucleotides, AntisenseRNA, MessengerRNA, Viral

Identifiers

PMID34285203
PMCPMC8292409
OpenAlexW3090618517

What OpenQuestion holds

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Registered trials

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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.