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Beyond A, G, C and U

Make the most out of mRNA
   



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Chemically modified mRNAs (referred to as syn-mRNAs or cmRNAs) have marked a revolution by bringing gene therapy in reach of clinical application. In syn-mRNAs, naturally occurring nucleobases of mRNA are partially or quantitatively replaced by modified analogs, while the eukaryotic 5'-cap is preserved[1]. Capped and internally modified RNAs of virtually any size can be obtained in a single-step procedure by in vitro transcription, employing the "anti-reverse cap analogue" (ARCA)[2] as an initiator and suitable triphosphates as elongators. In result, syn-mRNAs of exceptionally high translational efficiency[3] and low immunogenity[4] are becoming available in a scaleable manner for application as RNA vaccines[5] and for reprogramming approaches in stem-cell therapy[6].

Scheme 1: Starting from a suitable DNA template, syn-mRNAs are produced in vitro by phage RNA polymerases, such as T7 RNAP. While the eukaryotic 5' cap is introduced by transcriptional priming with ARCA, the analogs 5-methyl-CTP (m5CTP), pseudo-UTP (ψ), 2-Thio-UTP (s2UTP) and N6-methyl-ATP (m6ATP) are incorporated concomitantly in transcriptional elongation, thereby generating transcripts with superior pharmacological features.


Nucleotide analogs for mRNA Modification available from Jena Bioscience:

Compound

Cat. No.

Amount

Price (€)

m27,3'-OGP3G (ARCA Cap Analog)

NU-855-1

1 mg

100,45

NU-855-5

5 mg

454,08

m27,3'-OGP3G (ARCA Cap Analog)
solution

NU-855S

10 µl (100 mM)

77,55

NU-855L

5 x 10 µl (100 mM)

349,00

5-Methyl-CTP
Recently highlighted in [7-9]

NU-1138S

10 µl (100 mM)

110,05

NU-1138L

5 x 10 µl (100 mM)

322,36

N6-Methyl-ATP

NU-1101S

10 µl (100 mM)

53,77

NU-1101L

5 x 10 µl (100 mM)

196,00

Pseudo-UTP

NU-1139S

10 µl (100 mM)

63,59

NU-1139L

5 x 10 µl (100 mM)

287,00

2-Thio-UTP
Recently highlighted in [7-9]

NU-1151S

10 µl (100 mM)

53,77

NU-1151L

5 x 10 µl (100 mM)

196,00


Please refer to [7-9] for recent applications of our products in the design of optimized syn-mRNA sequences and the development of innovative transfection strategies.


Selected References:
[1] Quabius and Krupp (2015) Synthetic mRNAs for manipulating cellular phenotypes: an overview. New Biotechnology 32 (1):229.
[2] Stepinski et al. (2001) Synthesis and properties of mRNAs containing the novel anti-reverse cap analogs 7-methyl (3'-O-methyl)GpppG and 7-methyl (3'-deoxy)GpppG. RNA 7:1486.
[3] Karikó et al. (2008) Incorporation of Pseudouridine into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability. Mol. Ther. 16 (11):1833.
[4] Karikó et al. (2005) Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. Immunity 23:165.
[5] Petsch et al. (2012) Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 8:1210.
[6] Warren et al. (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 8:618.
[7] Ferizi et al. (2016) Human cellular CYBA UTR sequences increase mRNA translation without affecting the half-life of recombinant RNA transcripts. Sci. Rep. 6:39149.
[8] Badieyan et al. (2016) Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration. J. Control. Release 239:137.
[9] Utzinger et al. (2017) cmRNA/lipoplex encapsulation in PLGA microspheres enables transfection via calcium phosphate cement (CPC)/PLGA composites. J. Control. Release 249:143.

   
   
   
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