A chicken bioreactor for efficient production of functional cytokines

The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside of the US market, is compromised by the high cost of manufacture and validation compared to traditional chemical drugs. Improvements in transgenic technologies allow valuable proteins to be produced by genetically-modified animals; several therapeutic proteins from such animal bioreactors are already on the market after successful clinical trials and regulatory approval. Chickens have lagged behind mammals in bioreactor development, despite a number of potential advantages, due to the historic difficulty in producing transgenic birds, but the production of therapeutic proteins in egg white of transgenic chickens would substantially lower costs across the entire production cycle compared to traditional cell culture-based production systems. This could lead to more affordable treatments and wider markets, including in developing countries and for animal health applications. Here we report the efficient generation of new transgenic chicken lines to optimize protein production in eggs. As proof-of-concept, we describe the expression, purification and functional characterization of three pharmaceutical proteins, the human cytokine interferon α2a and two species-specific Fc fusions of the cytokine CSF1. Our work optimizes and validates a transgenic chicken system for the cost-effective production of pure, high quality, biologically active protein for therapeutics and other applications

A novel 4.1 ezrin radixin moesin (FERM)-containing protein, ‘Willin’

AbstractThe 4.1 superfamily of proteins contain a 4.1 Ezrin Radixin Moesin (FERM) domain and are described as linking the cytoskeleton with the plasma membrane. Here, we describe a new FERM domain-containing protein called Willin. Willin has a recognizable FERM domain within its N-terminus and is capable of binding phospholipids. Its intra-cellular distribution can be cytoplasmic or at the plasma membrane where it can co-localize with actin. However, the plasma membrane location of Willin is not influenced by cytochalasin D induced actin disruption but it is induced by the addition of epidermal growth factor

The intracellular interactions of the L1 family of cell adhesion molecules

The L1 family of CAMs (cell adhesion molecules) has long aroused the interest of researchers, but primarily the extracellular interactions of these proteins have been elucidated. More recently, attention has turned to the intracellular signalling potentiated by transmembrane proteins and the cytoplasmic proteins with which they can interact. The present review brings up to date the current body of published knowledge for the intracellular interactions of L1-CAM family proteins and the potential importance of these interactions for the mechanisms of L1-CAM action.</p