Related Experiment Video
Updated: Jun 29, 2025
10:02
Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
Published on: June 10, 2022
2.2K
A novel deep generative model for mRNA vaccine development: Designing 5' UTRs with N1-methyl-pseudouridine
Xiaoshan Tang1, Miaozhe Huo2, Yuting Chen1
1Institute of Systems Genetics, Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, China.
Acta Pharmaceutica Sinica. B
|April 4, 2024
Summary
Designing optimal 5' untranslated regions (UTRs) for N1-methyl-pseudouridine modified mRNA vaccines is crucial. A new machine learning tool, Smart5UTR, identifies superior 5' UTRs, enhancing vaccine efficacy against SARS-CoV-2 variants.
Area of Science:
- Molecular Biology
- Vaccinology
- Bioinformatics
Background:
- Efficient translation via the 5' untranslated region (UTR) is key for mRNA vaccine efficacy.
- N1-methyl-pseudouridine (m1Ψ) modification in mRNA impacts 5' UTR translation efficiency.
- Optimal 5' UTRs for m1Ψ-modified mRNA differ from unmodified mRNA.
Purpose of the Study:
- To develop a specialized tool for designing optimal 5' UTRs for m1Ψ-modified mRNA.
- To address the limitations of using high-expression endogenous gene 5' UTRs for m1Ψ-modified mRNA vaccines.
- To improve mRNA vaccine development through superior 5' UTR design.
Main Methods:
- Development of a novel machine learning-based tool, Smart5UTR.
- Utilizing a deep generative model for *in silico* identification of superior m1Ψ-5' UTRs.
- Employing a tailored loss function and network architecture in Smart5UTR.
Main Results:
- Smart5UTR successfully designs superior 5' UTRs for m1Ψ-modified mRNA.
- Smart5UTR overcomes limitations of existing design models.
- Smart5UTR-designed 5' UTRs significantly enhanced antibody titers for COVID-19 mRNA vaccines against Delta and Omicron variants.
Conclusions:
- Smart5UTR is a valuable tool for designing effective m1Ψ-5' UTRs for mRNA vaccines.
- Optimized 5' UTRs significantly boost mRNA vaccine performance.
- This approach holds great promise for advancing mRNA vaccine technology.
Keywords:
5′ UTRCOVID-19Machine learningN1-Methyl-pseudouridineSARS-CoV-2Sequence designmRNA designmRNA vaccineMore Related Videos
Related Concept Videos
02:27Nonsense-mediated mRNA Decay
10.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K
02:28Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
02:31Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
02:51mRNA Stability and Gene Expression
5.6K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.6K
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
9.3K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
9.3K
02:01pre-mRNA Processing
52.9K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
52.9K