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Abstract

Grant Number:	2R44GM064261-02
PI Name:	ZHU, LEI
PI Email:	lzhu@origentherapeutics.com
PI Title:
Project Title:	An Expression System for Protein Production in Eggs

Abstract: DESCRIPTION (provided by applicant): The recent and impending approval of monoclonal antibodies for therapeutic application challenges the capacity of conventional cell culture-based production systems to deliver adequate amount of these proteins. Origen Therapeutics' embryonic stem cell-mediated transgenesis technology offers an alternative production system. The protein can be specifically expressed in the oviduct and deposited into egg white. Large quantities of protein can be easily purified from egg white in a timely fashion. The aim of this research is to develop an oviduct-specific expression system for the ultimate goal of producing pharmaceutical proteins including monoclonal antibodies in eggs of transgenic chickens using Origen Theapeutics' technology. Specifically, monoclonal antibody expression vectors with regulatory sequences of the ovalbumin gene will be introduced into chicken ES cells for making high-grade chimeras and transgenic chickens that deposit monoclonal antibodies in egg white. The expression of the transgene will be determined in terms of tissue specificity and the levels of protein deposited in eggs. Methods for purification of monoclonal antibodies from eggs will be developed. The purified proteins will be subjected to detailed analysis to characterize posttranslational modification and biological activity. The end point of this research is a truly tissue-specific and yet high yield expression system that facilitates production of new pharmaceutical proteins. The system is scalable, rapid and will produce proteins with minimum expense.

Thesaurus Terms:
drug design /synthesis /production, egg /ovum, genetic regulation, genetic regulatory element, ovalbumin, protein biosynthesis, protein purification, recombinant protein, technology /technique development, transfection /expression vector
biotherapeutic agent, chemical structure function, high throughput technology, hormone regulation /control mechanism, posttranslational modification, protein localization, protein signal sequence, reporter gene, reproductive hormone, transgenic animal
biotechnology, chicken, embryonic stem cell, gene targeting, genetic library, tissue /cell culture

Institution:	ORIGEN THERAPEUTICS
	1450 ROLLINS RD
	BURLINGAME, CA 940102307
Fiscal Year:	2003
Department:
Project Start:	01-SEP-2001
Project End:	30-APR-2005
ICD:	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG:	ZRG1

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