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mRNA Modification

Modification of mRNA is essential to improve mRNA stability, translation efficiency and immunogenicity, which are important for the development of effective mRNA-based therapies and vaccines. Creative Biogene offers customized mRNA modification services to help customers produce transcripts suitable for downstream applications and facilitate the development and progression of their mRNA programs.

Why mRNA Modification is Important?

Some key points regarding the importance of mRNA modifications include the following:

  • Stability

mRNA is very susceptible to rapid degradation by nucleases in the cytoplasm. mRNA modifications, such as cap analogs and poly(A) tails, can increase the stability of mRNA by protecting it from degradation.

  • Translation efficiency

mRNA modifications can also enhance the translation initiation process and improve protein expression by optimizing the 5'-untranslated region (UTR) of mRNA.

  • Immunogenicity

mRNA-based therapies, such as mRNA vaccines and protein replacement therapies, can elicit immune responses in vivo. mRNA modifications can reduce the immunogenicity of mRNA by reducing the activation of innate immune receptors and increasing the stability of mRNA in the cytoplasm.

  • Codon optimization

Codon optimization involves replacing codons that are rarely used in human cells with codons that are more commonly used. This can improve the efficiency of mRNA translation and reduce the likelihood of premature termination.

  • Poly(A) tail length

The length of the poly(A) tail can also affect the stability and translation efficiency of mRNA. Shortening the poly(A) tail can increase the degradation of mRNA, while lengthening it can improve the translation efficiency.

Fig. 1 Immunogenicity of mRNAs after chemo-enzymatic modification at the 5′ cap.Fig. 1 Immunogenicity of mRNAs after chemo-enzymatic modification at the 5′ cap. (Van, et al., 2021)

mRNA Modification Service at Creative Biogene

Creative Biogene has developed a variety of mRNA modification technologies, including:

  • Synthesis of "cap"-like structures and "capping enzymes" to stabilize mRNA.
  • Adding regulatory sequences to the 5' and 3' UTR regions to stabilize mRNA.
  • Modifying the poly-A "tail" to stabilize mRNA and enhance protein translation.
  • Modifying nucleotides to reduce innate immune activation.
  • Isolation and/or purification techniques: Reducing immune activation and improving translation using RNase III treatment and fast protein liquid chromatography (FPLC) purification.
  • Optimization of sequences and codons, selection of codons homologous to tRNA, and improvement of translation rates.
  • Regulation of target cells: co-delivery of translation initiation factors and other methods to optimize translation and immunogenicity.

Creative Biogene's proprietary capping technology enables efficient and cost-effective co-transcriptional capping during in vitro transcription. In addition, our experienced scientists will provide customized mRNA modification strategies to maximize application-specific activity based on your project development demands.

Why Choose Us?

  • Multiple modification options for you to find the best GMP synthesis.
  • Customized services to meet diverse applications and demands.
  • Competitive pricing and fast turnaround times.

Creative Biogene's experienced experimental experts can guide your mRNA modification process, providing the best design and strategy for your GMP mRNA production. We offer a wide range of flexible mRNA modification options to best meet your demands for any project. Please feel free to contact us if you have a need, and our experienced specialists will be happy to assist you.

Reference:

  1. Van, Dülmen. M.; et al. Chemo-Enzymatic Modification of the 5' Cap Maintains Translation and Increases Immunogenic Properties of mRNA. Angew Chem Int Ed Engl. 2021 Jun 7;60(24):13280-13286.
* For research use only. Not intended for any clinical use.
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