Evidence map›Paper›PMID 38014203›Full record

ArticlebioRxiv : the preprint server for biology2023

Creation of de novo cryptic splicing for ALS/FTD precision medicine.

Oscar G Wilkins, Max Z Y J Chien, Josette J Wlaschin, Maria Pisliakova, David Thompson, Holly Digby, Rebecca L Simkin, Juan Antinao Diaz, Puja R Mehta, Matthew J Keuss and 10 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 2 countries.

Oscar G WilkinsUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Max Z Y J ChienUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Josette J WlaschinEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Bethesda, MD 20892, USA.
Maria PisliakovaUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
David ThompsonMammalian Genetics Unit, MRC Harwell Institute; Oxfordshire, OX11 0RD, UK.
Holly DigbyThe Francis Crick Institute; London, NW1 1AT, UK.
Rebecca L SimkinUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Juan Antinao DiazEGA-Institute for Women's Health, University College London; London, WC1E 6HX, UK.
Puja R MehtaUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Matthew J KeussUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Matteo ZanovelloUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Anna-Leigh BrownUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Peter HarleyUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Annalucia DarbeyUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Rajvinder KardaEGA-Institute for Women's Health, University College London; London, WC1E 6HX, UK.
Elizabeth M C FisherUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
Tom J CunninghamMammalian Genetics Unit, MRC Harwell Institute; Oxfordshire, OX11 0RD, UK.
Claire E Le PichonEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Bethesda, MD 20892, USA.
Jernej UleThe Francis Crick Institute; London, NW1 1AT, UK.
Pietro FrattaUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL; London, WC1N 3BG, UK.
MRC Prion Unit · GBThe Francis Crick Institute · GBFaculty of 1000 (United Kingdom) · GBKing's College London · GBMary Lyon Centre at MRC Harwell · GBNational Institutes of Health · US

Funding

The neuronal stress response in neurodegenerative disease and painZIAHD008966 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LE PICHON, CLAIRE · 2017 to 2025
$17.1M
Human Biomarkers CoreU54NS123743 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2021 to 2025
$8.2M
Intramural NIH HHS ZIA HD008966Medical Research Council MR/S006508/1NINDS NIH HHS U54 NS123743Wellcome Trust
6 · The paper itself

Abstract

A system enabling the expression of therapeutic proteins specifically in diseased cells would be transformative, providing greatly increased safety and the possibility of pre-emptive treatment. Here we describe "TDP-REG", a precision medicine approach primarily for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which exploits the cryptic splicing events that occur in cells with TDP-43 loss-of-function (TDP-LOF) in order to drive expression specifically in diseased cells. In addition to modifying existing cryptic exons for this purpose, we develop a deep-learning-powered algorithm for generating customisable cryptic splicing events, which can be embedded within virtually any coding sequence. By placing part of a coding sequence within a novel cryptic exon, we tightly couple protein expression to TDP-LOF. Protein expression is activated by TDP-LOF

Identifiers

PMID38014203
PMCPMC10680699
OpenAlexW4388713724

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.