2OmRNA

2OmRNA refers to a chemically modified form of ribonucleic acid in which the 2' hydroxyl group of the ribose sugar is replaced by a methoxy group, a modification more formally known as 2'-O-methyl RNA or 2'-OMeRNA. This modification is commonly introduced at one or more positions during solid-phase synthesis using 2'-O-methyl phosphoramidites, allowing researchers to tailor the properties of the RNA molecule for specific applications. 2OmRNA is not typically found in natural transcripts but is widely used in synthetic oligonucleotides.

The 2'-O-methyl modification has several notable effects on RNA chemistry. It increases resistance to nucleases, enhancing stability in biological environments. It generally elevates duplex thermal stability when paired with complementary RNA, and it can alter the geometry of base pairing to influence binding affinity. In therapeutic contexts, 2'-O-methyl modifications often reduce recognition by innate immune receptors such as Toll-like receptors, lowering immunogenicity. However, because 2'-O-methylated DNA-like segments usually do not promote RNase H activity, designs that rely on RNase H-mediated cleavage commonly incorporate a central DNA or other motif to recruit the enzyme in antisense applications.

Common uses of 2OmRNA include research reagents for stabilizing RNA duplexes, antisense oligonucleotides, and certain small interfering RNA (siRNA) constructs where enhanced stability and reduced immunogenicity are desired. The modification can affect the choice of design strategy, particularly regarding mechanisms of action such as RNase H recruitment versus steric blocking. In practice, 2OmRNA is one of several sugar-modified nucleic acids leveraged to optimize performance in RNA-based technologies.