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mRNA Therapeutics are Hot-Enter the Promise of Circular RNA

Bloomberg Businessweek October 4, 2021 pp39-40 |Solutions| “Running Circles Around mRNA” “Ring-shaped RNA may make the leap from vaccines to cancer treatments” THE BOTTOM LINE “Investors have poured more than $100 million into Orna’s reengineering of RNA strands from straight lines into circular-shaped RNA with the hope of creating new and inexpensive cancer treatments”

Read Bloomberg Businessweek for all the details.

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The success of mRNA vaccines has driven “venture capitalists to pour huge sums into startups focusing on transforming straight RNA strands into circles.” Discovered way back in 1995 new early-stage studies now suggest that the longer life of circular RNA may facilitate treatments of “cancer, autoimmune disorders and genetic diseases.” As of 2019 more than 32,000 "naturally-occurring" circulating RNA (circRNA) had been described (Sarter, Barr and Thum 2019).

Standard mRNA which is linear with two open ends is degraded in a relatively short time by RNA digesting enzymes. Such timing did not diminish the effectiveness of stimulating immunity against COVID but is considered insufficient for treating other diseases. Orna Therapeutics, Inc (Cambridge MA) has developed a method to create circRNA “ programming RNA with genetic code that instructs a line to split into several strands and then repair itself in the shape of a circle.”

So far using circular RNA, dubbed o-RNA by Orna, to treat diseases is unproven and “none of the projects in development has been tested in humans.” Another big hope, is that the o-RNA process may be easier and less expensive to use because the body…[does]...all the work.” Others, like Alex Wesselheoft et al. working in the field have also been “able to program RNA lines to cut themselves up and then come back together in the shape of a circle” but admit that getting it to work is “...a little bit more of an art than science” currently. Others who have discussed the work with Wesselheoft, like Danie Anderson (MIT), have commented that the system is just “an incredibly robust, straightforward scalable system that’s an order of magnitude cheaper than conventional modified RNA.

Figure from Molecular Therapeutics 2019 by Sarter, Bar and Thum. Proposed mechanisms for the formation of circRNA in the body. This team noted that more than 32,000 circRNA had been annotated as of their publication.


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