2' O-Methyl RNA (2' Me) Synthesis

2′-O-Methyl RNA is a naturally occurring RNA modification commonly found in tRNA and other small RNAs as part of post-transcriptional processing. Synthetic oligonucleotides containing 2′-O-Methyl RNA can be readily produced for research and therapeutic applications.

2′-O-methyl RNA (often written 2′-OMe RNA or 2′-O-methylated RNA) is an RNA molecule where the hydroxyl group (-OH) on the 2′ carbon of the ribose sugar has been chemically modified into a methoxy group (-OCH₃).

In normal RNA:

$\text{Ribose 2'}-OH \rightarrow 2'\text{-}OCH_3$

That small change has major effects on RNA behavior.

This modification increases the melting temperature (Tm) of RNA duplexes, enhancing binding affinity, while causing only minimal changes to RNA duplex stability. In addition, 2′-O-Methyl RNA exhibits strong resistance to degradation by single-stranded ribonucleases and is typically 5–10 times more resistant to DNase activity compared to unmodified DNA.

Due to its enhanced stability and affinity, 2′-O-Methyl RNA is widely used in antisense oligonucleotides, siRNA, and other RNA-based therapeutics. To designate a 2′-O-methyl modification within an RNA sequence, place a lowercase “m” before the modified nucleotide. For example: mAmGmCmU.

What it does

2′-O-methyl modification makes RNA:

• More resistant to degradation by nucleases
• More chemically stable
• Less immunogenic (less likely to trigger innate immune responses)
• Often better at binding targets in antisense or siRNA applications

Where it occurs naturally

2′-O-methylation is found naturally in:

• rRNA
• tRNA
• snRNA
• some mRNA caps
• viral RNAs

Cells use enzymes called methyltransferases to add the methyl group.
 

Why it matters in therapeutics

This modification is heavily used in:

• siRNA therapeutics
• antisense oligonucleotides (ASOs)
• CRISPR guide RNAs
• mRNA therapeutics and vaccines

because it improves stability and reduces immune activation.
 

Structural consequence

Regular RNA has:

• a reactive 2′-OH group

2′-OMe RNA replaces that with:

• 2′-O-CH₃

which decreases susceptibility to hydrolysis and changes sugar puckering/conformation.
 

Important distinction

“2′-O-methyl RNA base” is slightly imprecise terminology.

The methyl group is attached to the:

• ribose sugar
  not
• the nitrogenous base itself.

So:

• adenine, cytosine, guanine, uracil remain the same bases
• the sugar attached to them is modified

Product Information

 

Product Name:

2' O-Methyl RNA (2' Me) Synthesis

Category:

Modified sugar base

Modification Code:

[mA], [mG], [mC], [mU]

Structure:

Purification:

HPLC or PAGE

Delivery Format:

Lyophilized

Shipping Conditions:

Room Temperature

Storage Conditions:

-20°C To -70°C
Oligonucleotides are stable in solution at 4°C for up to 2 weeks. Properly reconstituted material stored at -20°C should be stable for at least 6 months. Dried DNA (when kept at 20°C) in a nuclease-free environment should be stable for years.

References/Citations:

• Freier SM, Altmann KH. Nucleic Acids Research (1997)
• Kurreck J. European Journal of Biochemistry (2003)
• Khvorova A, Watts JK. Nature Biotechnology (2017)
• Crooke ST. Nucleic Acid Therapeutics (2017)
• Motorin Y, Helm M. WIREs RNA (2011)
• Judge AD, et al. Molecular Therapy (2006)
• Hendel A, et al. Nature Biotechnology (2015)

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