In this Q&A, David Butler, chief technology officer at Hongene Biotech answers three key questions to provide more detail about the partnership.
Hongene Biotech
We recently announced that we’ll be joining forces with ReciBioPharm to deliver a gene editing development and manufacturing solution. This strategic partnership leverages our single guide RNA (sgRNA) synthesis technology and ReciBioPharm's comprehensive contract development and manufacturing organisation (CDMO) services to streamline the development process.
How did the ReciBioPharm partnership develop and what do you hope to achieve?
The partnership with ReciBioPharm began over a year ago when we visited their Watertown facility in the US to explore potential opportunities. We were very impressed with their state-of-the-art facilities and technical strength. Subsequent discussions led to this partnership, which provides a comprehensive CDMO solution under one roof for the gene editing field.
ReciBioPharm was already an established mRNA CDMO and gene editing solutions provider, however, they lacked what is arguably the most critical component for gene editing drugs – sgRNA. Hongene is able to provide that missing piece, backed by our expertise and over 25 years of experience in RNA manufacturing. Our method of sgRNA synthesis offers advantages over traditional methods, including reduced impurities and improved quality, at a competitive price point for customers. Together, we are aiming to redefine gene editing development and manufacturing with a complete and fully integrated CDMO package delivered from ReciBioPharm’s Watertown site.
How does Hongene's sgRNA synthesis process differ from traditional methods and what advantages does this approach offer?
The main challenge in sgRNA synthesis using traditional methods is achieving high purity material. Traditional manufacturing involves a lengthy chemical process whereby the sgRNA – which can be more than 100 nucleotides long – is synthesised one nucleotide at a time, presenting many opportunities for impurities to form and accumulate. These impurities are challenging to control during synthesis and even harder to remove during downstream purification.
Hongene’s sgRNA synthesis method uses a chemoenzymatic ligation technology that overcomes the challenges associated with traditional methods. We begin by synthesising shorter (fragment) oligonucleotides, which contain fewer impurities that are easier to control as compared to longer oligonucleotides. These fragments are then joined together in a reaction using an enzyme called ligase. Many impurities present in the fragments are not ligated during this process because they aren’t viable substrates for the enzyme. Such impurities are then easily removed during chromatographic purification, resulting in sgRNA with purities typically exceeding 90%. This is a significant improvement over traditional synthesis methods, where achieving even 80% purity is a challenge. Another advantage of our approach is its modularity, which allows us to synthesise sgRNA molecules in excess of 200 nucleotides in length, whilst maintaining similarly high levels of purity.
In our partnership, we will provide ReciBioPharm with fragment oligonucleotides and an optimised chemoenzymatic ligation process, from which they will synthesise the sgRNA at their Watertown facility. This key component will then be included in assembly of gene editing drugs.
How can this collaboration model shape the future of gene editing drug development and manufacturing?
This collaboration model can shape the future of gene editing drug development and manufacturing by providing customers with a vastly improved and streamlined solution for their programs.
Manufacturing gene editing drugs is complex for companies currently because they must navigate a fragmented supply chain involving multiple partners and stakeholders. Our collaboration aims to simplify this process by bringing together all key components and expertise in the same facility, easing the complexities and risks associated with the existing paradigm. By consolidating the supply chain, we can mitigate potential disruptions and delays which will expedite timelines, reduce costs and enhance overall efficiency.
The gene editing drug landscape is quite literally evolving rapidly, with novel modalities and other technologies emerging from research labs with some regularity. New companies form around these advances, which present business opportunities and associated market potential. Ultimately, these innovations will lead to the development of life-changing gene editing therapies, but the current manufacturing landscape can be very challenging for drug developers to navigate, with risk of patients not receiving therapies on time. The partnership between Hongene and ReciBioPharm recognizes the value of collaboration in this dynamic field to substantially mitigate these risks.
Manufacturing at ReciBioPharm’s Watertown site will benefit US-based gene editing developers initially but there is the potential to extend its advantages globally. As the gene editing market expands, such partnerships will become increasingly important for optimising drug development and shaping the future of this transformative field.