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Cap analogs with a photo-cleavable group as a general reagent to produce light-activatable mRNAs as tool for fundamental and medical research

Periodic Reporting for period 1 - FlashCaps (Cap analogs with a photo-cleavable group as a general reagent to produce light-activatable mRNAs as tool for fundamental and medical research)

Reporting period: 2022-05-01 to 2023-10-31

Messenger RNAs (mRNAs) have recently entered the stage as therapeutic modality. Examples are the mRNA-based vaccines against infection by SARS-Cov2. Hundreds of research groups in academia and industry aim to better understand the multiplicity of the mRNA technology and its possible applications. However, at present researchers are unable to control when and where the mRNA is translated into proteins – which then have a pharmacological effect. This is a bottleneck that severely limits the research needed to further develop mRNA as a therapeutic modality.

We present FlashCaps, the first applicable solution that allows mRNA studies to be driven by light without altering the structure or sequence of the natural mRNA. Light is an excellent external control element that can be applied with high precision in space and time and without interfering with cellular processes. FlashCaps prevent the translation of the mRNA until activated by light. FlashCaps are compatible with all standard mRNA production and application procedures and thus of interest to all research groups and companies working on mRNA to date.

In this proof of concept, we determine the innovation potential of FlashCaps with a team of highly qualified scientists and innovation managers. Technological research to ensure reproducibility, stability, scalability, and quality of FlashCaps will be performed. User-friendly applicability of FlashCaps is achieved through the involvement of beta-testers. Innovation management research, including market analyses, data analytics and consumer interviews, is conducted to define the potential customers and their needs, to analyse the market potential and to investigate our competitors. Based on the research results and the agile exchange between the technological and innovation management research, we will decide on the best way of knowledge transfer to make FlashCaps available to the growing number of mRNA researchers.
We performed technical research to upscale the synthesis of FlashCaps in a reproducible manner. We tested the stability of FlashCaps and found that they are highly stable as a solid. For our customers, we prepared detailed SOPs and manuals on how to use FlashCaps for the preparation of photocaged mRNA.
With respect to innovation management, we performed a market and competitor analysis. We acquired new customers and beta-testers by phone calls, presentations on scientific and marketing conferences and via our public website (https://flash-caps.de/(opens in new window)).
The University of Muenster filed international patent applications. We prepared NDAs with multiple customers and provided them with samples of FlashCaps as well as with technical support and personal feedback. To date, more than five beta-testers from academic and industrial labs obtained our FlashCaps .
Academic and industrial research labs are interested in the FlashCap-technology. The potential to precisely control when and where an mRNA is translated into the corresponding protein is huge. The main impact will be in basic science to better understand the effects of controlled mRNA expression. In addition, FlashCaps have potential for therapeutic applications. Here, however, a cap 1-derived FlashCap will be desirable. Future work should aim at synthesizing such a FlashCap.
In this proof-of-concept, we demonstrated that the synthesis of FlashCaps is robust and can be upscaled to supply the compound to several academic and industry partners. For optimal performance of FlashCaps when used by customers, the application should become easier. A complete kit (i.e. containing all buffers, enzymes and reactions vessels) instead of FlashCaps alone, will facilitate successful application of FlashCaps and reduce hesistations to use the new technology.
Flash-Caps: the first applicable solution that allows mRNA studies to be driven by light.
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