Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess Niklas Thalén1, Mona Moradi Barzadd1, Magnus Lundqvist1, Johanna Rodhe3, Monica Andersson3, Gholamreza Bidkhori2,4, Dominik Possner3, Chao Su3, Joakim Nilsson3, Peter Eisenhut5,6, Magdalena Malm1, Jeanette Westin3, Johan Forsberg3, Erik Nordling3, Adil Mardinoglu2, Anna-Luisa Volk1, Anna Sandegren3, Johan Rockberg1,* 1 Dept. of Protein science; KTH - Royal Institute of Technology; Stockholm; SE-106 91; Sweden 2 Science for Life Laboratory; KTH - Royal Institute of Technology; Solna; 171 65; Sweden 3 SOBI AB, Tomtebodavägen 23A, Stockholm, Sweden 4 AIVIVO Ltd. Unit 25, Bio-innovation centre, Cambridge Science park, Cambridge, UK. 5 ACIB - Austrian Centre of Industrial Biotechnology, Krenngasse 37, 8010 Graz, Austria 6 BOKU - University of Natural Resources and Life Sciences, Department of Biotechnology, Vienna, 1190, Austria * To whom correspondence should be addressed: Tel: +46 8 790 99 88; Email:
[email protected] Target journal: Cell Systems Take home message: • Transcriptomic comparison of two CHO clones with different productivities showed three genes relevant for sulfatase activation and secretion • Co-expression of genes with sulfatase led to a 150-fold increase in specific activity • Reduced promoter strength increased specific activity of sulfatase SUMMARY Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available.