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Optimising mRNA for Therapeutics: The Synergy of CleanCap® Technology and Minimal UTRs

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By Tebubio, October 2024

An Insight from the Tebubio Team
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Discover how minimal UTRs combined with CleanCap® technology are revolutionising mRNA-based therapeutics by enhancing mRNA stability, translation, and reducing immune interference risks. Take advantage of all the best tools in one place to advance your mRNA therapeutic research with Tebubio.

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"The minRNA allows therapeutics development without the need to design UTRs anymore. It means saving many months of research. MinRNA would become the highway to success."
Dimitri Szymczak
Dimitri Szymczak, PhD
Scientific Support Team at Tebubio

mRNA and UTRs: Unlocking New Frontiers in Therapeutic Innovation

Over the past five years, there has been an explosive surge in scientific interest surrounding messenger RNA (mRNA), as this small but powerful molecule has emerged as a pivotal player in the development of groundbreaking therapies.

Once viewed primarily as a transient intermediary in protein synthesis, mRNA is now recognised as a transformative tool, offering immense potential in vaccines and treatments for a range of complex diseases.

To produce messenger RNA, cells transcribe a portion of DNA into RNA, which will then be translated into proteins. mRNA consists of two main parts: coding regions, which specify the protein to be produced, and UnTranslated Regions (UTR), which are located at the ends (5′ and 3′) of the mRNA but do not code for the protein. These UTR regions play several essential roles in the regulation of mRNA, such as its transport, stability, and translation efficiency.

Maximising mRNA Efficiency for Therapeutic Applications: The Impact of Minimal UTRs

Schematic representation of messenger RNA (mRNA) structure with UTRs or minimal UTRs¹ 

To fully leverage the potential of mRNA in therapies and vaccines, it’s essential to explore the structural elements that contribute to its functionality, particularly the pivotal role of UTRs (mRNA stability, transport, and translation). These UTRs can inhibit mRNA expression in target cells, and the main challenge for researchers has been to identify the most suitable UTRs that maximise mRNA expression levels.

 

 

However, when using mRNA for therapies or vaccines, it is critical to ensure that the mRNA is rapidly and efficiently translated into protein. Research has shown that minimal UTRs (streamlined, shortened and optimised versions of the untranslated regions) of mRNA can significantly enhance:

 

  • mRNA Stability: Reduces the presence of sequences that could activate mRNA degradation mechanisms.
  • mRNA translation efficiency: Ensures that the translation machinery interacts quickly with the mRNA, without encountering regulatory sequences that slow down the process.
  • Reduction of immune interference risks: Avoids long and complex sequences that may be recognized as foreign patterns by the immune system.
 
The discovery of these minimalist UTRs and so minimalist RNA (minRNA) now spares researchers the tedious process of UTR optimisation, streamlining their efforts in mRNA-based therapeutics studies.

Enhancing mRNA Performance: The Complementary Duo of CleanCap and Minimal UTRs

Building on the importance of UTRs, it’s equally essential to consider how advanced technologies like CleanCap® capping during In Vitro Trascription (IVT) can further enhance mRNA stability and functionality.

CleanCap® and minimal UTRs are complementary strategies that optimise mRNA production at various stages of maturation and regulation. CleanCap® boosts mRNA stability and translation efficiency, while minimal UTRs streamline mRNA for better performance. Together, these approaches create more robust mRNA with accurate translation and extended cellular lifespan, reducing the risk of unwanted immune responses. This combination is vital for maximising therapeutic efficacy in mRNA-based therapeutics.

Tebubio: Faciliting Your Research with One-Stop Access

The Tebubio Contract Research Services (CRS) team would be delighted to assist you with the construction of your plasmid template, offering services such as codon optimisation, gene synthesis, cloning, plasmid preparation and minimalistic RNA.

Tebubio’s scientific experts can source all the lipids you need for your LNP formulation projects.

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Are you interested in optimising your mRNA stability and translation efficiency with CleanCap® Technology?

 

We offer, all in one place, a comprehensive range of reagents optimised and validated for CleanCap® M6, namely:

 

 

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References & Sources

  1. Mamaghani S, Penna RR, Frei J, Wyss C, Mellett M, Look T, Weiss T, Guenova E, Kündig TM, Lauchli S, et al. Synthetic mRNAs Containing Minimalistic Untranslated Regions Are Highly Functional In Vitro and In Vivo. Cells. 2024; 13(15):1242. https://doi.org/10.3390/cells13151242

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