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Development and differentiation of hyperstable consensus monobodies based on the type 3 fibronectin domain

thesis
posted on 26.07.2021, 06:50 by PETER GEOFFREY CHANDLER
Monobodies based on the type 3 fibronectin (FN3) domain are designed to overcome limitations of the antibody binding scaffold, being more simple and more amenable to the rigours of drug development. This thesis focuses on the development of FN3Con, a hyperstable consensus FN3 monobody. Through grafting of binding loops from monobodies of median stability, this work produced two FN3Con constructs with affinity to clinical targets and a shelf life of over 2 years at room temperature. The thesis then investigates methods to meaningfully differentiate monobodies from the antibody scaffold through buffer excipients, chemical conjugation and integration of native fibronectin characteristics.

History

Principal supervisor

Ashley Buckle

Additional supervisor 1

Sheena McGowan

Additional supervisor 2

Remy Robert

Year of Award

2021

Department, School or Centre

Biochemistry and Molecular Biology

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine, Nursing and Health Sciences