Wyss Institute launches RNA therapeutics startup EnPlusOne Biosciences

By Elissa Wolfson, The Science Advisory Board assistant editor

December 21, 2022 -- Wyss Institute at Harvard University has partnered with Northpond Labs to launch EnPlusOne Biosciences. The startup aims to bring versatile, scalable RNA synthesis technology to market, with the goal of unlocking the development of new RNA drugs, vaccines, and gene-editing therapies.

EnPlusOne Bio's worldwide exclusive licensing agreement with Harvard grants it the rights to commercialize a novel, controlled enzymatic RNA oligonucleotide synthesis (ezRNA) technology. The ezRNA platform technology was invented and advanced by a team of biologists, chemists, and life science entrepreneurs at Wyss, with support from Northpond Labs, the research and development affiliate of Northpond Ventures.

Although RNA oligonucleotide synthesis by chemical methods has enabled many valuable discoveries and disease treatments over the past 50 years, current production techniques limit its advancement. By leveraging proprietary enzymes and nucleic acid building blocks, EnPlusOne Bio aims to overcome current challenges in RNA therapeutics manufacturing. These challenges include the efficient synthesis of long RNA sequences (>120 nucleotides), the installation of therapeutic nucleic acid modifications for stabilization and delivery purposes, and large-scale (>1 kg) RNA production.

According to the Wyss Institute and EnPlusOne Bio, the advantages of ezRNA technology over traditional methods are that it can be performed independently of a template nucleic acid sequence, and that all reactions take place in water under mild conditions.

Water-based reactions not only allow access to novel nucleotide building blocks that are impossible or difficult to incorporate into RNA using current chemical techniques, but they also reduce the use of environmentally harmful chemicals.

EnPlusOne CEO Daniel Wiegand, formerly of Wyss, said the new company's plans include building out a pilot lab over the next two years and expanding the capabilities of the technology.

"The development of this technology, which is both powerful and environmentally friendly ... should provide a significant boost to the RNA therapeutics field and result in major advances in the treatment of various diseases," Wyss founding director and Harvard professor Dr. Donald Ingber said in a statement.

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