Main — General Oligo, Inc.

General Oligo (“GO”) is dedicated to advancing nucleic acid technology through precision design, sustainable manufacturing, and open collaboration. Founded in early 2025, we combine expertise in nucleic acid chemistry, oligonucleotide synthesis, and synthetic biology with a commitment to developing practical, reliable products for life science research.

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Publication

Template-independent enzymatic synthesis of RNA oligonucleotides

RNA oligonucleotides have emerged as a powerful therapeutic modality to treat disease, yet current manufacturing methods may not be able to deliver on anticipated future demand. Here, we report the development and optimization of an aqueous-based, template-independent enzymatic RNA oligonucleotide synthesis platform as an alternative to traditional chemical methods. The enzymatic synthesis of RNA oligonucleotides is made possible by controlled incorporation of reversible terminator nucleotides with a common 3′-O-allyl ether blocking group using new CID1 poly(U) polymerase mutant variants. We achieved an average coupling efficiency of 95% and demonstrated ten full cycles of liquid phase synthesis to produce natural and therapeutically relevant modified sequences. We then qualitatively assessed the platform on a solid phase, performing enzymatic synthesis of several N + 5 oligonucleotides on a controlled-pore glass support. Adoption of an aqueous-based process will offer key advantages including the reduction of solvent use and sustainable therapeutic oligonucleotide manufacturing.

June 12, 2026

Daniel Wiegand, MS ChE

Founder, Principal Engineer

Richie Kohman, PhD

Scientific Advisor

George Church, PhD

Scientific Advisor

Daniel Wiegand, MS ChE

Founder, Principal Engineer

Daniel Wiegand is a synthetic biologist, chemical engineer, and entrepreneur. During his nearly decade-long tenure (2013-2022) as a member of the Advanced Technology Team at the Wyss Institute for Biologically Inspired Engineering at Harvard University, he worked on array-based oligonucleotide synthesis, nucleic acid-based data storage, engineering novel RNA polymerases, and next-generation sequencing chemistries. He went on to co-found EnPlusOne Biosciences in 2022, serving as its inaugural CEO, raising $12M in seed financing, and leading development of its enzymatic oligonucleotide synthesis platform for scaled manufacturing of RNA therapeutics. Daniel is an alumnus of the Nucleate program (cohort 2020) and holds a B.S. in Biochemistry and M.S. in Chemical Engineering from Northeastern University.

Richie Kohman, PhD

Scientific Advisor

Richie Kohman is an inventor, scientist, and research institute executive with over 15 years of experience building and leading high-risk, high-reward research programs across academic, industrial, and nonprofit settings. As Lead of the Synthetic Biology Platform at Harvard's Wyss Institute for Biologically Inspired Engineering, he worked alongside Dr. George Church to advance programs spanning nucleic acid synthesis, next-generation sequencing, gene editing, and genome engineering. He subsequently served as Chief Scientific Officer of the Wyss Center for Bio and Neuroengineering in Geneva, overseeing a broad portfolio of translational neurotechnology and synthetic biology programs. He also served as co-PI of the IARPA MICrONS project, one of the largest efforts to map synaptic connectivity in the brain. Richie holds a Ph.D. in Organic Chemistry from the University of Illinois Urbana-Champaign.

George Church, PhD

Scientific Advisor

George Church is the Robert Winthrop Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard and MIT, and a founding member of the Wyss Institute for Biologically Inspired Engineering. Widely regarded as a founder of modern genomics, he developed the first direct genome sequencing method, co-initiated the Human Genome Project, and launched the Personal Genome Project. At the Wyss Institute, he directs the Synthetic Biology Platform, where his lab has pioneered enzymatic nucleic acid synthesis, genome engineering, and novel biopolymers. His innovations form foundational pillars of the synthetic biology field, and his laboratory has catalyzed the founding of more than 50 biotechnology companies spanning gene therapy, RNA therapeutics, genome sequencing, and synthetic biology. He is elected to the National Academies of Sciences and Engineering and has co-authored 782 papers and 170 patent publications, including the book Regenesis.

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📍 Somerville, MA, USA
✉ info@generaloligo.com

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Template-independent enzymatic synthesis of RNA oligonucleotides

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