In comparison to neutral linear polymers, functional and architecturally complex (i.e., non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them in vivo are scarce. This presentation will cover this important topic with emphasis on two types of therapeutic proteins: ones for which long circulation in the bloodstream is desired, and ones for which retention and/or stabilization in the gastrointestinal tract is desired.
We will first present how the modification of an enzyme with a polymer of appropriate architecture can impart exceptionally low immunogenicity (e.g., generation/recognition of antibodies in vivo), with a commensurably low loss of therapeutic activity[1],[2]. Secondly, we will also discuss how the modification of an enzyme with a polymer bearing appropriate functional groups can promote its stability (and thus therapeutic activity) at different locations in the gastrointestinal tract. Furthermore, functional polymers that interact with mucin will be shown to promote retention in the upper part of the gastrointestinal tract, and thus enhance the therapeutic activity of enzymes at this location[3]. Overall, the importance of the findings will be framed with context to selected relevant diseases that stand to benefit most from the presented concepts.
This work was supported by the Swiss National Science Foundation (310030_135732) and the Sassella Stiftung.
References:
[1] Liu, Tirino, Radivojevic, Phillips, Gibson, Leroux, Gauthier. Advanced Functional Materials. 2013, 23, 2007.
[2] Liu, Johansen, Zabel, Leroux, Gauthier. Nature Communications.
[3] Fuhrmann, Grotzky, Lukić, Matoori, Yu, Luciani, Walde, Schlüter, Gauthier, Leroux. Nature Chemistry, 2013, 5, 582.