Scientific advances in gene cloning and recombinant DNA technology have enabled researchers to genetically engineer proteins and growth factors that can be used to develop new therapies. By isolating and manipulating genes that code for human proteins, it is now possible to mass produce these proteins using bacterial or mammalian cell systems. This recombinant protein approach has revolutionized biotechnology and generated thousands of new products across many industries.
In the pharmaceutical sector, recombinant techniques allow for the large scale manufacturing of human proteins that were previously only available in limited quantities from biological sources. One such clinically important protein is human epidermal growth factor or EGF. EGF plays a crucial role in cell growth and proliferation and has significant therapeutic potential.
Discovering the Potential of EGF
Epidermal growth factor was first identified in the early 1960s from extracts of male mouse submaxillary glands. It was found to promote the proliferation of epithelial cells and fibroblast cells. Subsequent research revealed that EGF is a small, single chain polypeptide consisting of 53 amino acids. It functions by binding to epidermal growth factor receptors (EGFR) that are present on the surface of many cell types. This binding activates intracellular signaling pathways that regulate key cellular functions involved in growth, differentiation and survival.
The potential medical uses of EGF became apparent once its molecular structure and mechanism of action were uncovered. It was hypothesized that administering EGF could help accelerate wound healing by stimulating the growth of epithelial and connective tissue cells at injury sites. Initial clinical studies found EGF to be effective in promoting wound closure, re-epithelialization and granulation in burns, ulcers, and other types of chronic wounds. However, developing a large-scale production process for this promising protein proved challenging due to its small quantities in natural sources.
Making Recombinant Human EGF a Commercial Reality
In the mid-1980s, Genentech scientists were the first to synthesize the human EGF gene and use recombinant DNA techniques to produce it in bacteria. This represented a major breakthrough that opened the door for a scalable biomanufacturing process. Genentech initially turned to E. coli bacteria to mass-produce the protein as it was easy to genetically engineer. However, obtaining properly folded active EGF from E. coli remained difficult due to differences in mammalian and bacterial protein processing machinery.
In the late 1980s, Genentech optimized recombinant human EGF (rhEGF) production using mammalian CHO cells. These Chinese hamster ovary cells have the cellular components necessary to correctly fold and secrete human proteins. Large-scale growth of CHO cells in bioreactors now generates clinical grade rhEGF on an industrial scale. Genentech's milestone achievements in cloning the EGF gene and establishing a robust manufacturing system paved the way for rhEGF to advance to clinical use.
Driving Commercial Success in Wound Healing Applications
The launch of Regranex gel containing rhEGF as the active ingredient was a major commercial success for Genentech. Approved by the FDA in 1998, it became the first recombinant protein pharmaceutical used for wound care. Numerous clinical studies demonstrated that Regranex accelerated the closure of chronic lower extremity diabetic ulcers when standard care had failed. This provided physicians and patients with an effective new option that had been unavailable before the advent of genetic engineering.
Regranex enjoyed blockbuster sales exceeding $200 million at its peak, capturing an important therapeutic niche. However, its use gradually declined due to the emergence of cheaper wound care alternatives. Nonetheless, Regranex helped validate the clinical utility of growth factor therapy and proved that recombinant proteins could find markets in less glamorous areas beyond oncology. Its legacy lives on as biopharmas continue exploring the wound healing potential of various growth factors.
Shaping the Biotech Landscape
Genentech's pioneering research on rhEGF in the 1980s played an instrumental role in the rise of the modern biotechnology industry. It served as a powerful proof-of-concept demonstrating that genetic engineering could unlock new classes of protein therapeutics. Their groundbreaking work attracted significant investment and enabled biotech to evolve from a fledgling science experiment into a full-fledged commercial endeavor.
The success of Regranex in the late 1990s further validated biologics as a viable therapeutic modality. It showcased the commercial potential for using cell culture to manufacture drugs that were previously scarce in nature. Overall, rhEGF developments established Genentech as the industry trailblazer and paved the way for countless other recombinantly produced proteins that transformed medicine in the following decades. Genentech's accomplishments with EGF thus mark a seminal chapter in biotechnology’s ongoing transformation of healthcare.
In Summary, the production of recombinant human epidermal growth factor involves sophisticated biotechnological processes that ensure purity, potency, and safety. Through recombinant DNA technology, rhEGF can be produced in large quantities with consistent quality, making it a reliable source for medical and cosmetic applications.
