Startup aims to bring a versatile, sustainable, and scalable RNA synthesis technology to market to unlock development of new RNA drugs, vaccines, and gene-editing therapies
By Benjamin Boettner
(BOSTON) — Today, the Wyss Institute for Biologically Inspired Engineering at Harvard University and EnPlusOne Biosciences (EnPlusOne Bio) announced that the startup company has signed a worldwide, exclusive licensing agreement with Harvard’s Office of Technology Development (OTD) that grants EnPlusOne Bio the rights to commercialize a novel, controlled enzymatic RNA oligonucleotide synthesis technology. The “ezRNA” platform technology was invented and advanced by Wyss Core Faculty member George Church, Ph.D. and an expert team of biologists, chemists, and life science entrepreneurs at the Wyss Institute, and 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.
“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.
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.
He is also a Professor of Genetics at Harvard Medical School (HMS) and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT). He leads the Wyss Institute’s Synthetic Biology Platform and has co-founded multiple startups to commercialize technologies spawned by groups at the Wyss Institute and HMS.
Strong technology and team building
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 (> 1kg).
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.
“EnPlusOne Bio is a true success story of the Wyss Institute’s translation model: the concept for EnPlusOne Bio started as a causal conversation between two colleagues in the laboratory, gained significant support for technological de-risking and commercialization by key players in the Harvard ecosystem, and ultimately became its own company,” said Daniel Wiegand, M.S.Ch.E., a former member of the Synthetic Biology Platform at the Wyss Institute who is now the CEO of EnPlusOne Bio. “The team and I are also incredibly grateful for the opportunity to work with Northpond Labs as part of the alliance between Northpond Labs and the Wyss Institute. This alliance has allowed us to maximize our value before exiting the Wyss’ labs, and positioned EnPlusOne Bio with an excellent chance at success. We will be building out a pilot lab over the next two years and expanding the capabilities of the technology.”
In addition to Wiegand, the technology was developed and de-risked at the Wyss Institute by Jonathan Rittichier, Ph.D., a former Wyss Postdoctoral Fellow and now the company’s CSO; Howon Lee, Ph.D., another former Postdoctoral Fellow at the Wyss; Dan Ahlstedt, M.B.A. 2021, who joined the team as a Harvard Business School Blavatnik Fellow in Life Science Entrepreneurship and became the company’s COO; as well as Ella Meyer, who was introduced to the Wyss team as an intern by Northpond Ventures and then joined EnPlusOne Bio as a Research Associate. EnPlusOne was co-founded by Church, Wiegand, Rittichier, Ahlstedt, and Lee.
Empowering support
Greatly facilitating its path to commercialization, the project and team that became EnPlusOne Bio were selected in 2019 for funding by the Wyss’ competitive Validation Project program, which was renewed in 2020. Beyond the walls of the Wyss, in 2020 the team also joined the Nucleate Program. The future EnPlusOne Bio team was named the “most investable” team by venture capitalists at the VC Pitch Competition in Nucleate’s MedTech category.
Importantly, also in 2020, EnPlusOne Bio’s technology became the first Wyss project to be supported by Northpond Labs via the Laboratory for Bioengineering Research and Innovation at the Wyss Institute. In addition to providing financial support, Northpond Ventures also provided business and strategy guidance to the EnPlusOne Bio team in coordination with the Wyss’ business development unit, facilitating EnPlusOne Bio’s spin-out from the Wyss Institute and positioning it for significant impact in the RNA therapeutics market. Additionally, Northpond Ventures led a syndicate of investors in financing EnPlusOne Bio’s series seed financing.
We believe EnPlusOne Bio’s technology can fundamentally improve the way RNA therapeutics and vaccines are designed and manufactured […] I anticipate EnPlusOne Bio will be the first of many innovative companies that will be co-created by the Wyss Institute-Northpond Labs alliance.
“We believe EnPlusOne Bio’s technology can fundamentally improve the way RNA therapeutics and vaccines are designed and manufactured. The Wyss Institute-Northpond Labs alliance enables the translation of science out of the lab and the co-creation of companies that are ready for seed-stage funding by investors. I anticipate EnPlusOne Bio will be the first of many innovative companies that will be co-created by the Wyss Institute-Northpond Labs alliance,” said Michael Rubin, M.D., Ph.D., CFA, Founder and CEO of Northpond Ventures.
“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 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, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.