Identification of peptides that bind growth plate chondrocytes by phage display: a first step toward targeted therapy.

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NIDCD	ENDOC-4

* FARE Award Winner

Authors

• C.S. Cheung
• J.C. Lui
• J. Baron

Abstract

Mutations in genes that regulate the growth plate cause skeletal dysplasias, in which the bones are short and malformed, leading to serious disability. In the past decade, our understanding of growth plate biology has remarkably expanded, and yet translation of the experimental findings into effective treatment strategies for skeletal dysphasia still remains very limited. This is largely because most regulators of the growth plate involve local, paracrine growth factors, which do not lend themselves to therapeutic applications. However, we envision that these locally-acting molecules could be linked to cartilage-targeting peptides and administrated systemically, augmenting treatment efficacy and lowering off-target effects. We therefore sought to identify such peptides with high binding affinity and specificity to allow targeted therapy using phage display. After 3 rounds of selection, resulting phage clones demonstrated increased affinity to chondrocytes by ELISA, compared to insertless phage. Furthermore, those selected phage showed little preferential binding to other cell types, including skin fibroblasts, myocytes and hepatocytes in comparison to insertless phage, suggesting a tissue-specific interaction. Immunostaining result revealed that the peptide-displaying phage bound to the cell surface of chondrocytes. Further investigation is now ongoing to determine the binding affinity, tissue specificity and precise molecular targets of the free peptides.

back to top