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- Thalén, Niklas, 1985-, et al.
(författare)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 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. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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- Reyes Forsberg, Diana, et al.
(författare)
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A method for chemical and physical modification of oriented pulp fibre sheets
- 2022
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Ingår i: Cellulose. - : Springer Science and Business Media B.V.. - 0969-0239 .- 1572-882X. ; 29:15, s. 8371-8386
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Tidskriftsartikel (refereegranskat)abstract
- Wood pulp fibres are promising reinforcements for biocomposites due to their renewable resource origin and mechanical properties. An oriented and dense fibre reinforcement structure is beneficial for biocomposite properties. We present a method of modifying fibres (e.g. to increase strain to failure) in pre-formed oriented high-density paper structures intended for biocomposites or as hot-pressed fibre materials. Mildly delignified, well-preserved holocellulose fibres from softwood are used. Cold alkali treatment (hemicellulose removal) and mercerisation (conversion to cellulose II) were carried out successfully on oriented fibre sheets. Controlled anisotropy and sheet density are achieved from untreated and straight fibres in the sheet formation step. High mechanical properties and increased ductility of mercerised sheets were observed, which may be valuable for hot-pressed fibre materials (E ≈ 7.1 GPa, strength of 108 MPa and strain to failure of 5.3%) and biocomposites. In contrast, modified wood pulp fibres were difficult to orient, resulting in higher sheet porosity and weak interfibre bonding. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s).
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