The Wyss Institute for Biologically Inspired Engineering at Harvard University is partnering with Northpond Labs to launch the RNA synthesis company EnPlusOne Biosciences (EnPlusOne Bio). EnPlusOne Bio aims to bring a scalable RNA synthesis technology to market to unlock the development of new RNA drugs, vaccines, and gene-editing therapies.

The startup company signed an exclusive licensing agreement with Harvard’s Office of Technology Development that grants EnPlusOne Bio the rights to commercialize a novel, controlled enzymatic RNA oligonucleotide synthesis technology—the “ezRNA” platform technology—developed by George Church, PhD, professor at Harvard Medical School and Wyss Core Faculty member.

“My own early work on highly modified RNAs going back to 1973, and in vivo and in vitro chemistry for nucleic acid synthesis and modifications that I later developed with my lab finds a new and clinically highly relevant continuation in EnPlusOne’s approach, which could revolutionize the creation of future RNA therapeutics,” said Church, who co-founded EnPlusOne.

Although the synthesis of RNA oligonucleotides by chemical methods has enabled many valuable discoveries and novel ways to treat disease throughout the past 50 years, the future promise of RNA is limited by current production techniques. By leveraging a toolbox of proprietary enzymes and nucleic acid building blocks, EnPlusOne Bio aims to overcome current challenges in the manufacturing of RNA therapeutics. These range from the efficient synthesis of long RNA sequences (>120 nucleotides), to the installation of therapeutic nucleic acid modifications for stabilization and delivery purposes, and producing RNA at very large scales (> 1 kg).

The key advantages of the controlled enzymatic RNA oligonucleotide synthesis technology over traditional methods are that it can be performed independently of a template nucleic acid sequence, and all reactions take place under mild conditions in water. The upside of water-based reactions is two-fold: they reduce the use of environmentally harmful chemicals, creating a “greener” approach to RNA synthesis, and they allow access to novel nucleotide building blocks that are not possible or very difficult to incorporate into RNA using current chemical techniques.

“We are incredibly proud of EnPlusOne Bio launching out of the Wyss Institute. The development of this technology, which is both powerful and environmental-friendly, and the formation of an outstanding team at the Institute with major support and partnership from Northpond Labs in our strategic alliance, should provide a significant boost to the RNA therapeutics field and result in major advances in the treatment of various diseases,” said Wyss founding director Donald Ingber, MD, PhD, who is also a professor of vascular biology at Harvard Medical School.

The work was supported and funded by Northpond Labs, the research and development-focused affiliate of Northpond Ventures, as the inaugural project of the Wyss Institute-Northpond Labs alliance.

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