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Nucleotides Modification

Background Nucleotides Modification Services Highlights FAQs Published Data

Background

As a world-leading services provider, Creative Biolabs is dedicated to providing a full range of customized nucleotides modification services for worldwide clients based on the value of time-saving and cost-effective manner.

  • Overview of Nucleotides Modifications

When it comes to the bio-molecular modifications, the first thing that comes to mind is the post-translational modification of proteins, which has been indicated to exert essential roles in a variety of signaling pathways, cellular activities, and many other biological functions. However, it has been found that post-translational modification is not only the "privilege" of proteins, but also occurs in other biomolecules in the organism, such as DNA and RNA. And post-transcriptional modification of RNA can enhance the stability of RNA structure, improve the efficiency of translation, and increase the structural and functional diversity of RNA.

RNA modification generally refers to the alterations (mainly addition and substitution) of chemical groups on four RNA bases and the ribose sugar moiety, leading to the secondary/tertiary structures and functions change of RNAs. Currently, there are at least 170 types of RNA modifications have been discovered in all living organisms. These modified RNAs are widely distributed in all kinds of RNAs, among which ribosomal RNA (rRNA) and transfer RNA (tRNA) are the most heavily modified. The base type, location, and quantity of the modifications all have an impact on the stability, activity, recognition, localization of RNAs, and they may also be related to some human diseases.

Internal RNA modification can modify site.

Fig.1 Internal RNA modifications.1

Nucleotides Modification Services

Nucleotides modifications affect a diversity of biological processes in the organisms. For instance, modifications (commonly N⁶-methyladenosine) in messenger RNA (mRNA) regulate various aspects, such as mRNA location, metabolism, stability, protein translation, even stem cell differentiation. Chemical modifications in tRNA and rRNA directly affect protein translation. In humans, these diverse modifications in RNAs are closely linked to some human disorders, such as tumors and cancers, neurological disorders, mitochondrial-linked diseases, and diabetes.

All these properties and critical bio-functions endow the RNA modification of great potential to be a useful tool in laboratory analysis and therapeutics development. Firstly, the modified RNAs can be used for the control of gene expression and cell differentiation in epigenetics research, also can be utilized for RNA structure optimization. More importantly, the development of these nucleotides modifications or effective inhibitors holds great potential in human disease treatment.

Creative Biolabs provides a diversity of fully custom mRNA modification services based on the four basic base modifications as follows:

Pseudouridine(Ψ)

5-ribosyl isomer of nucleoside uridine

Pseudouridine

2-Thiouridine (s2U)

C-5 sulf-modified nucleoside uridine

2-Thiouridine

5-Methylcytidine (m5C)

C-5 methyl-modified nucleoside cytidine

5-Methylcytidine

N6-Methyladenosine (m6C)

N-6 methyl-modified nucleoside adenosine

N6-Methyladenosine
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Highlights

  • Fully customized: both single type modification and one-stop design to detection are all available
  • Well-established platform: equipped with advanced biological techniques and experienced scientist teams
  • Time-saving: rapid in silico prediction and bioinformatics analysis provide assistance
  • High performance: standard experimental procedures, professional staff, and abundant expertise offer the most optimized and tailored solutions

FAQ

Q: What is the purpose of nucleotide modifications in mRNA?

A: Nucleotide modifications enhance RNA stability, improve translation efficiency, and diversify RNA structures and functions.

Q: What types of nucleotide modifications are offered by Creative Biolabs?

A: We offer modifications such as pseudouridine, 2-thiouridine, 5-methylcytidine, and N6-methyladenosine.

Q: How do nucleotide modifications affect biological processes?

A: These modifications regulate mRNA location, metabolism, stability, protein translation, and stem cell differentiation.

Q: Can Creative Biolabs customize nucleotide modifications?

A: Yes, we provide fully customized services, including single-type modifications and comprehensive design-to-detection solutions.

Q: What is the significance of pseudouridine modification?

A: Pseudouridine enhances RNA stability and function by altering the structure of uridine.

Q: Can nucleotide modifications be combined in a single RNA molecule?

A: Yes, Creative Biolabs can incorporate multiple modifications in a single RNA molecule to achieve desired properties.

Published Data

The article investigates the effects of nucleoside modifications on mRNA transfection efficiency and immune activation in primary human monocytes and macrophages. The study specifically looks at modifications like pseudouridine and 5-methyl-cytidine, which are shown to reduce immune activation and increase cell viability compared to non-modified mRNA. Modified mRNA leads to lower expression of immune activation markers such as CD80 and reduced secretion of pro-inflammatory cytokines like TNF-α and IFN-β. This research underscores the importance of nucleoside modifications in enhancing the stability and efficacy of mRNA for therapeutic applications, particularly in immune cells.

Evaluation of the immunogenicity of cells using modified or unmodified mRNA encoding EGFP or mCherry.

Fig.2 Macrophages transfected with modified or non-modified mRNA encoding for either EGFP or mCherry.2

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References

  1. Barbieri, I.; Kouzarides, T. Role of RNA modifications in cancer. Nature Reviews Cancer. 2020, 1-20.
  2. Moradian, Hanieh, et al. "mRNA transfection-induced activation of primary human monocytes and macrophages: dependence on carrier system and nucleotide modification." Scientific reports 10.1 (2020): 4181.
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