AlbuCORE: an albumin-based molecular scaffold for multivalent biologics design.
MAbs
; 12(1): 1802188, 2020.
Article
de En
| MEDLINE
| ID: mdl-32816577
ABSTRACT
As biologics have become a mainstay in the development of novel therapies, protein engineering tools to expand on their structural advantages, namely specificity, affinity, and valency are of interest. Antibodies have dominated this field as the preferred scaffold for biologics development while there has been limited exploration into the use of albumin with its unique physiological characteristics as a platform for biologics design. There has been a great deal of interest to create bispecific and more complex multivalent molecules to build on the advantages offered by protein-based therapeutics relative to small molecules. Here, we explore the use of human serum albumin (HSA) as a scaffold for the design of multispecific biologics. In particular, we describe a structure-guided approach to the design of split HSA molecules we refer to as AlbuCORE, that effectively and spontaneously forms a native albumin-like molecule, but in a heterodimeric state upon co-expression. We show that the split AlbuCORE designs allow the creation of novel fusion entities with unique alternate geometries. We also show that, apart from these AlbuCORE fusion entities, there is an opportunity to explore their albumin-like small hydrophobic molecule carrying capacity as a drug conjugate in these designs.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Ingénierie des protéines
/
Multimérisation de protéines
/
Sérum-albumine humaine
Limites:
Humans
Langue:
En
Journal:
MAbs
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2020
Type de document:
Article
Pays d'affiliation:
Canada