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Research Update

5-Hydroxymethyl-dCTP: A New Tool for Epigenetic Research

The epigenome is responsible for memory formation, X chromosome activation and cellular differentiation. Though the field of epigenetics considers all factors that contribute to transcriptional regulation, DNA methylation is the most well recognized, particularly the methylation of cytidine to 5-methyl-dC within CpG sites.

Scientists are finding that DNA methylation is more dynamic than previously believed. Many are now researching the various mechanisms that regulate DNA methylation, seeking to advance regenerative medicine and stem cell reprogramming. Recently 5-Hydroxymethyl-dC has been acknowledged as a key player in epigenetics. Although its exact function is not known; it may influence chromatin structure and be involved in demethylation.

A mechanism for demethylation through oxidation is carried out by a family of proteins called TET. TET1 was first discovered in acute myeloid leukaemia (AML); the proceeding succession of studies found the TET family responsible for leukaemogenesis. Interestingly, 5-Hydroxymethyl-dU is a deamination intermediate in this oxidative demethylation pathway that ultimately converts 5-methyl-dC to C. In order to provide additional tools for epigenetics research, TriLink now offers both 5-Hydroxymethyl-dCTP (Cat # N-2060) and 5-Hydroxymethyl-dUTP (Cat # N-2059).

NTPs for Epigenetic Research
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Technology Spotlight

Advancing mRNA Therapeutics through Modification

The use of mRNA to affect gene expression has garnered significant interest recently as an alternative to DNA therapeutics, which are rife with safety concerns and high inefficiency. Inherently there is less risk of permanent damage or effect when influencing the transcriptome, rather than the genome. The potential downside is that most likely mRNA treatments would need to be administered indefinitely.

In a recent publication by Kormann et al. the improvement of therapeutic mRNA in vivo delivery by chemical modification was explored. Chemical modifications explored included pseudo-U, N6-methyl-A, 2-thio-U and 5-methyl-C. The team found that by substituting 25% of the uridine and cytidine with 2-thio-U and 5-methyl-C respectively, they were able to significantly decrease toll-like receptor mediated recognition of the mRNA in mice. By reducing the activation of the innate immune system, these modifications also increase the stability and longevity of the mRNA in vivo. Kormann et al. demonstrated the therapeutic efficacy of modified mRNA in a mouse model of a fatal human lung disease, administering the treatment by direct aspiration into the lungs and by intramuscular injection.

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Question of the Month

Q - I don’t see the modified nucleoside triphosphate that I need, can you make it for me?

A – Yes, if you don’t see what you need on our website or in our catalog, please inquire about our custom chemistry services. In addition to over 150 stocked modified nucleotides, TriLink offers custom polyphosphate synthesis, including mono-, di- and triphosphates. If the polyphosphate your research requires is not commercially available, our nucleic acid chemists are here to prepare it for you, even if there is currently no known synthesis scheme. You may provide your own nucleoside, we can purchase the nucleoside if it is commercially available or it can be prepared as a custom synthesis.

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