RNA drugs represent a promising frontier in medicine. However, the traditional method of manufacturing them is costly, labor-intensive, and environmentally harmful. Researchers have now developed a new enzyme-based RNA synthesis technique that enables the production of RNA strands with natural and modified nucleotides without the associated environmental risks.
While many people became familiar with RNA-based medicines through the COVID-19 vaccines, RNA oligonucleotides have been used for years to treat diseases like Duchenne Muscular Dystrophy and amyloidosis. RNA therapies offer numerous advantages over conventional small molecule drugs, including the ability to target genetic components within cells and guide gene editing tools like CRISPR.
Global demand for RNA is increasing rapidly, surpassing the industry’s manufacturing capabilities. The current method of chemically synthesizing RNA, developed in the 1980s, requires specialized equipment and generates significant amounts of toxic chemical waste, limiting production capacity and posing environmental risks. To address this challenge, a team of scientists from the Wyss Institute at Harvard University and Harvard Medical School has introduced an innovative enzyme-based RNA synthesis process. This method has the potential for rapid scalability and can incorporate a wide range of nucleotide building blocks without the environmental drawbacks associated with traditional chemical synthesis methods.
The researchers have established a more sustainable and efficient approach to RNA synthesis that relies on water and enzymes instead of toxic solvents and explosive catalysts. This novel method can accommodate the molecular modifications commonly used in RNA drugs and has the capacity to introduce new RNA chemistries for innovative therapies. The details of this breakthrough are published in a recent paper in Nature Biotechnology.
Recognizing the growing demand for RNA drugs, the researchers founded EnPlusOne Biosciences to commercialize this technology. Their enzymatic RNA synthesis approach represents a paradigm shift towards a more sustainable and aqueous manufacturing process, essential for meeting the increasing demand for RNA drugs.
A Sustainable Approach to RNA Synthesis
The team at the Wyss Institute, led by researchers Rittichier, Wiegand, and Kuru, identified the opportunity to revolutionize RNA synthesis using enzymes. By enhancing an enzyme from Schizosaccharomyces pombe, the team improved its efficiency to incorporate non-standard nucleotides into RNA strands. This modification was crucial for developing an effective drug development platform, as modified nucleotides are commonly used in FDA-approved RNA drugs to enhance stability and functionality.
Unlike traditional chemical synthesis methods that require the addition and removal of protective groups on nucleotides, the enzymatic approach developed by EnPlusOne eliminates the need for such steps, streamlining the manufacturing process. Although the enzyme initially posed challenges by stringing nucleotides uncontrollably, the researchers successfully addressed this issue by introducing a “blocker” mechanism to ensure precise nucleotide addition, simplifying the synthesis process.
The team demonstrated that their enzymatic synthesis process achieved a nucleotide incorporation efficiency of 95%, comparable to traditional chemical methods. By iteratively repeating cycles of enzymatic RNA synthesis, they were able to produce RNA molecules up to 23 nucleotides in length, suitable for many RNA therapeutics in the market.
Advancing RNA Therapeutics
One of the key aspects of RNA drug development is the ability to incorporate modified nucleotides. EnPlusOne’s enzymatic synthesis method has shown success in producing RNA strands with diverse modified nucleotides, expanding the possibilities for creating RNA molecules with unique functions and properties. This groundbreaking work has paved the way for commercialization, with EnPlusOne Biosciences aiming to revolutionize the production of RNA therapeutics.
The collaboration between the Wyss Institute, Northpond Labs, and other partners has enabled the validation and commercialization of this innovative enzymatic RNA synthesis approach. With the support of investors like Northpond Ventures, Breakout Ventures, and Coatue, EnPlusOne is driving the transformation of RNA drug manufacturing towards a more sustainable and efficient future.
Unlocking the Potential of RNA Therapeutics
EnPlusOne’s enzymatic synthesis platform offers a promising alternative to traditional chemical-based methods, providing a sustainable solution for producing high-quality RNA therapeutics. This innovative approach not only expands the chemical diversity of RNA drugs but also minimizes environmental impact while enabling the production of RNA molecules for various therapeutic applications.
The development of RNA drugs represents a significant advancement in treating a wide range of diseases. EnPlusOne’s enzymatic synthesis method has the potential to revolutionize the RNA therapeutics industry and accelerate the development of novel treatments, offering hope for improved healthcare outcomes.
This pioneering work, supported by the Wyss Institute at Harvard University and other partners, marks a significant leap forward in the field of RNA therapeutics, with the potential to benefit patients worldwide.
