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Drug Discovery

Orna Therapeutics launches with $80 million for circular mRNA therapies

The MIT spin-off says circularized mRNA therapies could be cheaper and more effective than linear mRNA

by Ryan Cross
February 25, 2021 | A version of this story appeared in Volume 99, Issue 7

A diagram showing three parts of circular RNA.
Credit: Orna Therapeutics
Orna’s circular RNA encodes a therapeutic protein (red), a site to initiate translation (yellow), and the remnants of a ribozyme (blue).

Orna Therapeutics has launched with $80 million in series A financing to develop a new version of messenger RNA (mRNA) therapies conceived in Daniel Anderson’s lab at Massachusetts Institute of Technology.

Not long ago, skepticism about mRNA therapies was pervasive in the drug industry. But the first two authorized mRNA products—the Pfizer-BioNTech and Moderna COVID-19 vaccines—have quelled questions about whether the technology works. Now a suite of private investors and drug companies—including Bristol Myers Squibb, Gilead Sciences, and Novartis—is betting that Orna has an even better way of making mRNA therapies.

The loose ends of linear mRNA molecules are susceptible to enzymatic degradation, making them short-lived. Anderson and his former PhD student R. Alexander Wesselhoeft thought that tying up those loose ends into a circle could help improve the stability of mRNA therapies.

To create mRNA circles, they designed linear mRNA with two ends that form a structure called a circularization ribozyme when they meet. That ribozyme cements the formation of the circle. Another segment called the internal ribosome entry sequence is used to initiate translation of the circularized mRNA in cells. After publishing the strategy in 2018, Anderson, Wesselhoeft, and others founded Orna in 2019 to develop the concept further.

Orna CEO Thomas Barnes claims that circular mRNA, which the firm has dubbed oRNA, has a number of advantages over linear mRNA, including better delivery into cells and better protein expression in cells. It could also be cheaper to manufacture since it doesn’t require the expensive caps added to the ends of linear mRNA therapies.

Barnes says Orna’s lead program uses oRNAs as an alternative to CAR T-cell therapies for cancer. oRNAs packaged in lipid nanoparticles can reach several immune cells—including T cells, natural killer cells, and macrophages—in the body, potentially providing an alternative to removing the cells and modifying them in the lab to target a person’s cancer, he says. The company is also interested in using oRNAs to deliver instructions for large proteins whose genes don’t fit inside the viral vectors currently used in gene therapy.



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