Clare Murray Ph.D. is Chief Executive Officer of EnPlusOne Biosciences, a Watertown, MA-based biotechnology company harnessing the power of enzymes to deliver better RNA at scale. Dr. Murray most recently served as Senior Vice President of Corporate Development and Operations at Life Edit Therapeutics, a gene editing discovery and development company she co-founded and scaled through acquisition by ElevateBio. Dr. Murray then also served as Head of Business Development and Strategy at ElevateBio.

Her leadership experience spans early-stage innovation through late-stage commercial partnerships, including senior roles at AgBiome, Aptuit, SCYNEXIS, and Novartis. Dr. Murray holds a B.Sc. in Chemistry and a Ph.D. in Synthetic Organic Chemistry from the University of Liverpool, and an MBA from the Fuqua School of Business at Duke University. She was also a Post-Doctoral Fellow at Washington University School of Medicine.

What is EnPlusOne’s mission and why is it so important?

Our mission is to enable the synthesis of pure and precise RNA for therapeutic use, at limitless scale.

Why is this important: The RNA therapeutics market is rapidly growing, including siRNA, ASOs, mRNA, gRNA for CRISPR and RNA editing modalities, and future modalities such as tRNA.

The success of genetic medicines has driven their adoption into chronic diseases with large patient populations, such as high cholesterol and liver disease. As a result, the number of approved RNA products has increased, leading to deeper pipelines of RNA therapeutics. Advances in delivery systems, such as the use of ligands like GalNAc to deliver to the liver, have also contributed to demand.

We now face an issue with the very chemistry that got us here. The current standard for RNA manufacturing cannot produce siRNA at needed levels or gRNA at required purity. Right now, it is impossible to synthesize human tRNA because harsh reaction conditions in that process destroy the complex modifications made by our body’s enzymes. Even more threatening for the field, phosphoramidite chemistry, the current standard, demands nonrenewable resources and requires stringent disposal.

The challenge is how to manufacture these very necessary therapeutics – both at the scale needed for some siRNA drugs, or the purity needed for gRNA, while overcoming the environmental issues presented by classical phosphoramidite chemistry.

EnPlusOne is going back to how nature makes RNA – using the sustainability, fidelity and mildness of enzymes in water that has produced all the RNA that’s ever been made organically. Our ezRNA platform will not only allow us to answer the needs coming from genetic medicines developers but will also open up a new RNA structural landscape for the discovery of additional innovative RNA therapeutics.

What does enzymatic synthesis of RNA bring to the life sciences industry?

Enzymatic synthesis will enable drug developers to deliver on the potential of RNA therapeutics to patients. Efficient manufacture of API has a direct impact on patient access to marketed drugs. We’ve seen the struggles in the cell and gene therapy field – with amazing therapeutics that can’t achieve their promise due to complex manufacturing needs. Our ezRNA platform with its purity and scale offers the chance for RNA therapeutics to reach every patient that needs them.

Tell us more about the proprietary technology that’s behind EnPlusOne’s advances. What’s the secret behind EnPlusOne’s breakthrough RNA technology?

Think of RNA as a pearl necklace. In nature, there are only four colors of pearls—just four RNA building blocks. But over the past few decades, scientists figured out how to make more colors in the lab –20 or more – and that unlocked RNA’s potential as a powerful new class of medicine.

The catch? To do it, they used toxic, messy, even explosive chemicals. And in the process, they lost the purity, precision, and elegance of how nature builds RNA.

That’s where EnPlusOne comes in.

We’ve developed a custom enzyme and the colorful RNA building blocks to go with it. Now we can bring the full color palette of chemistry to RNA but assemble it the way nature would: one clean, gentle, precise addition at a time.

Our platform combines the best of biology with the creativity of chemistry.

And we’re just getting started—because our enzyme is already showing us it can add new colors even chemistry hasn’t dreamed of.

Clare, as you’re taking on the CEO role, what do you see as some of the near-term goals for the company?

When I learned about the opportunity to join EnPlusOne a few months ago, I was working at a gene editing company and thus very aware of the landscape for gRNA synthesis and manufacture. EnPlusOne’s enzymatic approach caught my attention – I wanted to know if it was really feasible to make long lengths of RNA efficiently, with high purity, and without using large volumes of organic solvents. It turns out that it is, and that is what led me to accept the position.

Now that the platform has hit the next stage of development – high cycle efficiencies, high purity, incorporation of standard and novel modifications, and reasonable scale, we are actively developing collaborations with partners in the RNA therapeutics space.

Beyond that, what does EnPlusOne hope to achieve in the next few years?

We believe that the future of RNA manufacturing will be driven by enzymatic synthesis and that our proprietary technology will be embedded in the first-generation RNA therapeutics being developed today. We’re focused on bringing this reality to fruition while continuing to innovate with modifications that may enable us to help customers develop therapeutics for a wider range of diseases.

Can you share some upcoming milestones?

• Internal
  • Operational improvements as we scale
  • Synthesis efficiencies equal to or better than phosphoramidite
  • Explore novel modifications and delivery technologies

• External
  • Closing at least two new partnerships
  • Presenting at the 2025 Nature Conference, Cracking the Code: Nucleic Acid Medicines Coming of Age, in December. Organized by the leading siRNA and ASO companies
  • Participating in the top tier Oligonucleotide Therapeutics Society conference in October

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