Header

UZH-Logo

Maintenance Infos

Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo


Liu, Mi; Johansen, Pål; Zabel, Franziska; Leroux, Jean-Christophe; Gauthier, Marc A (2014). Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo. Nature Communications, 5:5526.

Abstract

In comparison to neutral linear polymers, functional and architecturally complex (that is, 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. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.

Abstract

In comparison to neutral linear polymers, functional and architecturally complex (that is, 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. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.

Statistics

Citations

10 citations in Web of Science®
14 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Date:2014
Deposited On:12 Feb 2015 14:00
Last Modified:08 Dec 2017 12:08
Publisher:Nature Publishing Group
ISSN:2041-1723
Publisher DOI:https://doi.org/10.1038/ncomms6526
PubMed ID:25407758

Download

Full text not available from this repository.
View at publisher