An international research team led by the University of Vienna has succeeded in developing a new version of RNA building blocks with higher chemical reactivity and photosensitivity. This can significantly reduce the production time of RNA chips used in biotechnological and medical research. The chemical synthesis of these chips is now twice as fast and seven times more efficient. About 40 years ago, a method was developed for the chemical synthesis of DNA and RNA, in which any sequence can be assembled from DNA or RNA building blocks using phosphoramidite chemistry. The assembly of a nucleic acid chain is carried out step by step using these special chemical building blocks (phosphoramidites). Each building block carries chemical 'protecting groups' that prevent unwanted reactions and ensure the formation of a natural link in the nucleic acid chain. While DNA microarrays are already widely used, adapting the technology to RNA microarrays has proved difficult due to the lower stability of RNA.

 

In 2018, the University of Vienna demonstrated how high-density RNA chips can be produced through photolithography: by precisely positioning a beam of light, areas on the surface can be prepared for the attachment of the next building block through a photochemical reaction. A team from the Institute of Inorganic Chemistry at the University of Vienna, in collaboration with the Max Mousseron Institute for Biomolecules at the University of Montpellier (France), has now developed a new version of RNA building blocks with higher chemical reactivity and photosensitivity. This advance significantly reduces the production time of RNA chips, making synthesis twice as fast and seven times more efficient. The innovative RNA chips can be used to screen millions of candidate RNAs for valuable sequences for a wide range of applications.

 

As a direct application of these improved RNA chips, the publication features a study of RNA aptamers, small oligonucleotides that specifically bind to a target molecule. Two "light-up" aptamers that produce fluorescence upon binding to a dye were chosen and thousands of variants of these aptamers were synthesized on the chip. A single binding experiment is sufficient to obtain data on all variants simultaneously, which opens the way for the identification of improved aptamers with better diagnostic properties.