Periodic Reporting for period 1 - Kyron.bio WomenTech (Cell line engineering for imporved fertility treatment)
Reporting period: 2023-07-01 to 2024-01-31
In the last decade, there has been an explosion in drug discovery. We are discovering and testing new molecules faster than ever before. However, bioproduction techniques are limiting advanced medicines from reaching patients.
Living cell factories are used to produce therapeutic proteins such antibodies, hormones and vaccines. Over 70% of these complex drugs are produced using mammalian cells, due to their ability to add complex modifications to the protein, more directly reflecting the patients natural biological processes and thereby enhancing clinical outcomes. However, mammalian systems underproduce complex proteins: they suffer from low productivity, typically producing protein at 10-100-fold lower yield of proteins than required (Jayapal et al.,). Approximately three quarters of therapeutic proteins are produced below the industry standard. Kyron.bio is making molecular level changes to improve the bioproduction efficiency, using synthetic biology.
The specific purpose of this grant is to focus our platform technology on optimising the production of Folicle Stimulating Hormone (FSH), a hormone that controls sexual functions and naturally stimulates the ovaries to produce eggs. FSH is administered during fertility treatment, and currently has a global market size of $41M. Current bioproduction tools are limiting optimal production of FSH: yield of FSH is 100 fold below the industry standard for biologics. Further, optimal molecular modifications are required to optimise pregnancy outcomes, with a 30% increase in pregnancy outcomes observed when women receive treatment with optimised FSH (Selman et al., 2010). Here, we propose the use of our novel proprietary cell line to optimise production of FSH.
Living cell factories are used to produce therapeutic proteins such antibodies, hormones and vaccines. Over 70% of these complex drugs are produced using mammalian cells, due to their ability to add complex modifications to the protein, more directly reflecting the patients natural biological processes and thereby enhancing clinical outcomes. However, mammalian systems underproduce complex proteins: they suffer from low productivity, typically producing protein at 10-100-fold lower yield of proteins than required (Jayapal et al.,). Approximately three quarters of therapeutic proteins are produced below the industry standard. Kyron.bio is making molecular level changes to improve the bioproduction efficiency, using synthetic biology.
The specific purpose of this grant is to focus our platform technology on optimising the production of Folicle Stimulating Hormone (FSH), a hormone that controls sexual functions and naturally stimulates the ovaries to produce eggs. FSH is administered during fertility treatment, and currently has a global market size of $41M. Current bioproduction tools are limiting optimal production of FSH: yield of FSH is 100 fold below the industry standard for biologics. Further, optimal molecular modifications are required to optimise pregnancy outcomes, with a 30% increase in pregnancy outcomes observed when women receive treatment with optimised FSH (Selman et al., 2010). Here, we propose the use of our novel proprietary cell line to optimise production of FSH.
The funding provided by the Women TechEU program allowed the CEO Dr. Emilia McLaughlin and Senior Scientist Dr. Marina Lochhead to complete a project to improve the production and performance of Follicle Stimulating Hormone (FSH), a hormone that controls sexual functions and naturally stimulates the ovaries to produce eggs. FSH is administered during fertility treatment, and currently has a global market size of $41M. Current bioproduction tools are limiting the optimal production of FSH: yield of FSH is 100-fold below the industry standard for biologics. Further, optimal molecular modifications are required to optimise pregnancy outcomes, with a 30% increase in pregnancy outcomes observed when women receive treatment with optimised FSH (Selman et al., 2010).
During this project, we used a novel glycan engineering approach to explore the role of N-glycosylation on FSH function, and developed a cell line that could be beneficial for FSH production.
During this project, we used a novel glycan engineering approach to explore the role of N-glycosylation on FSH function, and developed a cell line that could be beneficial for FSH production.
This project combined structure-based glycan engineering and genetically engineering mammalian cells to enhance the therapeutic activity of FSH. We showed that by engineering additional N-glycan sites into the β-subunit of FSH, we can modestly increase its bioactivity. We believe that through optimization of expression by generating cell lines stably expressing our glycan-engineered version of FSH that we can significantly improve its therapeutic potential and form the basis of the next-generation of FSH, in which the interaction between the ⍺-subunit and the β-subunit of FSH is the focal point of therapeutic improvement.