About: Theoretical basis for stabilizing messenger RNA through secondary structure design

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Theoretical basis for stabilizing messenger RNA through secondary structure design Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Theoretical basis for stabilizing messenger RNA through secondary structure design
Creator	Das, Rhiju Kim, Do Participants, Eterna Andres, R Wayment-Steele, Hannah Choe, Christian Huang, Po-Ssu Nicol, John Sperberg, Parra Wellington-Oguri, Roger
source	BioRxiv
abstract	RNA hydrolysis presents problems in manufacturing, long-term storage, world-wide delivery, and in vivo stability of messenger RNA (mRNA)-based vaccines and therapeutics. A largely unexplored strategy to reduce mRNA hydrolysis is to redesign RNAs to form double-stranded regions, which are protected from in-line cleavage and enzymatic degradation, while coding for the same proteins. The amount of stabilization that this strategy can deliver and the most effective algorithmic approach to achieve stabilization remain poorly understood. Motivated by the need for stabilized COVID-19 mRNA vaccines, we present simple calculations for estimating RNA stability against hydrolysis, and a model that links the average unpaired probability of an mRNA, or AUP, to its overall rate of hydrolysis. To characterize the stabilization achievable through structure design, we compare optimization of AUP by conventional mRNA design methods to results from the LinearDesign algorithm, a new Monte Carlo tree search algorithm called RiboTree, and crowdsourcing through the OpenVaccine challenge on the Eterna platform. Tests were carried out on mRNAs encoding nanoluciferase, green fluorescent protein, and COVID-19 mRNA vaccine candidates encoding SARS-CoV-2 epitopes, spike receptor binding domain, and full-length spike protein. We find that Eterna and RiboTree significantly lower AUP while maintaining a large diversity of sequence and structure features that correlate with translation, biophysical size, and immunogenicity. Our results suggest that increases in in vitro mRNA half-life by at least two-fold are immediately achievable and that further stability improvements may be enabled with thorough experimental characterization of RNA hydrolysis.
has issue date	2020-08-24(xsd:dateTime)
bibo:doi	10.1101/2020.08.22.262931
has license	biorxiv
sha1sum (hex)	8411b4c95511adab4a6e85bd1cca5c9b22b212c1
schema:url	https://doi.org/10.1101/2020.08.22.262931
resource representing a document's title	Theoretical basis for stabilizing messenger RNA through secondary structure design
schema:publication	bioRxiv
resource representing a document's body	covid:8411b4c95511adab4a6e85bd1cca5c9b22b212c1#body_text
is schema:about of	named entity 'calculations' named entity 'Tests' named entity 'vivo' named entity 'compare' named entity 'mRNAs' named entity 'probability' named entity 'stabilized' named entity 'hydrolysis' named entity 'mRNA' named entity 'enzymatic' named entity 'large' named entity 'biophysical' named entity 'receptor' named entity 'binding domain' named entity 'hydrolysis' named entity 'algorithm' named entity 'crowdsourcing' named entity 'mRNA' named entity 'optimization' named entity 'fluorescent protein' named entity 'design' named entity 'probability' named entity 'crowdsourcing' named entity 'COVID-19' named entity 'mRNA' named entity 'messenger RNA' named entity 'hydrolysis' named entity 'receptor binding domain' named entity 'COVID-19' named entity 'RNA' named entity 'secondary structure' named entity 'hydrolysis' named entity 'ribose' named entity 'secondary structure' named entity 'nucleotides' named entity 'nucleotides' named entity 'RNA hydrolysis' named entity 'ith' named entity 'conformation' named entity 'mRNA vaccine' named entity 'mRNA' named entity 'principal component analysis' named entity 'half-life' named entity 'allele' named entity 'innate immune response' named entity 'cleavage' named entity 'coding sequence' named entity 'mRNA' named entity 'structural properties' named entity 'transition state' named entity 'double-stranded' named entity 'pKa' named entity 'nucleotide' named entity 'sequence space' named entity 'mRNA' named entity 'phosphate' named entity 'epitope' named entity 'molecule' named entity 'mRNA' named entity 'chemical instability' named entity 'spike protein' named entity 'RNA' named entity 'CAI' named entity 'cleavage' named entity 'RNAs' named entity 'RNA' named entity 'codons' named entity 'RBD' named entity 'probability' named entity 'mRNA translation' named entity 'empirical knowledge' named entity 'vaccine design' named entity 'epitopes' named entity 'COVID-19 pandemic' named entity 'divide-and-conquer'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software