Photocage Cap for mRNAs

Short summary A German university has developed a process that provides mRNA with protection from proteases so that the mRNA can undergo the desired transformation in a cell. The scientists have built a protective cap into the mRNA. The University is offering companies a licensing agreement or a research cooperation agreement.

Full description mRNA is normally transformed in cells so that a protein is formed at the end. However, mRNAs are also susceptible to other proteins (proteases) and are usually only supposed to undergo the desired transformation in certain cells. To ensure that this works as desired, a protective cap was incorporated here at a reactive end of the mRNA. This protective cap can then be selectively cleaved off using light, so that the mRNA only completes its transformation in the desired cell. Almost all eukaryotic messenger RNAs (mRNAs) are modified at their 5'-ends by a cap that is synthesised by addition of a 7-methylguanosine attached via a 5'-5' triphosphate bridge to the first transcribed nucleotide of the mRNA chain. The cap structure plays a pivotal role in mRNA metabolism, mRNAs that carry a cap structure are efficiently translated (i.e. serve as template for protein synthesis). Cap analogues with different modifications have been developed. Modified caps and capped mRNAs can be employed to alter production of proteins in various eukaryotic in vitro translations systems and in cultured cells. Alternative strategies to further allow control of location and time of translation via caged nucleic acids have been developed. For this, numerous positions on nucleobases have been targeted, involving formal substitution of a hydrogen atom with a photocaging group. Such photo-caged caps, however, are an artificial compound in mRNA metabolism and will not yield the native nucleoside. The N7 position of guanosine and the N1 position of adenosine were also used for chemical modification with a photolabile caging group. However, photocaging groups derived from the ortho‐nitrobenzyl moiety were not suitable and did not yield the desired photocleavage to release guanosine. Additionally, the N7 position requires remethylation reducing the precision of time controlled translation. Therefore, it is an object of the present invention to provide a photocontrollable 5'-cap analogue, particularly a photocleavable 5'-cap analogue that allows for a regeneration of the native cap. The object is solved by a photocleavable-cap as shown in the Figure. The 5'-cap analogue consequently enables a photocontrollable translation with efficiencies similar to the natural process and has been shown in vitro, in cells and in vivo (Zebrafish). This application thus concerns a broad field and can be used in pharmaceutical as well as biotechnological research.This is mostly used in basic research but also already in some clinical studies.The University is offering interested companies a licensing agreement or a research collaboration.

Advantages and innovations The mRNA protection cap offers the following advantages: - High efficiency - Low toxicity - Novel access via conjugation of new photoactive cap - Compatible with normal IVT reaction
Contact / source: NEXT EEN Widgets (europa.eu)