Evidence map›Paper›PMID 38895198›Full record

ArticlebioRxiv : the preprint server for biology2024

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca

Rachael Miller, Joseph Paquette, Alexandra Barker, Ellen Sapp, Nicholas McHugh, Brianna Bramato, Nozomi Yamada, Julia Alterman, Dimas Echeveria, Ken Yamada and 5 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Rachael MillerRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.ORCID 0000-0002-4594-0640
Joseph PaquetteRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.
Alexandra BarkerRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.
Ellen SappMassGeneral Institute for Neurodegenerative Disease, 114 16 Street, Charlestown MA, 02129.
Nicholas McHughRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.
Brianna BramatoRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.ORCID 0000-0001-6966-7696
Nozomi YamadaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.
Julia AltermanRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.ORCID 0000-0002-6195-0857
Dimas EcheveriaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.
Ken YamadaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.ORCID 0000-0002-5714-8298
Jonathan WattsRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.ORCID 0000-0001-5706-1734
Christelle AnacletDepartment of Neurologic Surgery, University of California Davis School of Medicine, Davis, CA, 95618.ORCID 0000-0002-0526-8132
Marian DiFigliaMassGeneral Institute for Neurodegenerative Disease, 114 16 Street, Charlestown MA, 02129.
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.ORCID 0000-0001-6928-8071
Neil AroninRNA Therapeutics Institute, University of Massachusetts Chan Medical School, 368 Plantation Street, Worcester, MA, 01605.

Funding

Advancing RNA Therapeutics for Huntington’s DiseaseU01NS114098 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL · 2020 to 2024
$6.7M
Expanding the chemical diversity of therapeutic oligonucleotides to treat neurodegenerative disordersR01NS104022 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2017 to 2026
$6.0M
Chemical engineering of therapeutic RNAs for extrahepatic deliveryR35GM131839 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2019 to 2026
$3.1M
Selective Editing of the Mutant Huntingtin GeneR01NS106245 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL · 2018 to 2022
$2.4M
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
NIGMS NIH HHS R35 GM131839NIH HHS S10 OD020012NINDS NIH HHS R01 NS104022NINDS NIH HHS R01 NS106245NINDS NIH HHS U01 NS114098
6 · The paper itself

Abstract

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection. Electroencephalography (EEG) and electromyography (EMG) in awake mice demonstrated seizures. Using ion chromatography, we show that siRNAs can tightly bind Ca

Identifiers

PMID38895198
PMCPMC11185713

What Socratic 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 Socratic graph.