RDNA technique

Biotechnology is being appHed in the dairy industry. A significant and controversial development is the technique of producing transgenic animals, ie, animals in which hereditary deoxyribonucleic acid (DNA) has been augmented by DNA from another source, using recombinant DNA (rDNA) techniques. 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

While rDNA techniques offer exciting possibilities, there are many unanswered questions about the potential toxicity that each new product represents. For example, acute clinical toxicities of interferons (IFNs) include flu-like syndrome, fever, chills, malaise, anorexia, fatigue, and headache. Chronic dose-limiting toxicities include neutropenia, thrombocytopenia, impairment of myeloid maturation, reversible dose-related hepatotoxicity, some neurological toxicity (stupor, psychosis, peripheral neuropathy) and gastrointestinal toxicity. Some of these toxicities would be difficult to ascertain in rodents, and, in fact, may be species-specific. 

The basic process technology in vaccine production consists of fermentation for the production of antigen, purification of antigen, and formulation of the final vaccine, In bacterial fermentation, technology is well established. For viral vaccines, cell culture is the standard procedure. Different variations of cell line and process system are in use. For most of the live viral vaccine and other subunit vaccines, production is by direct infection of a cell substrate with the virus. Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous cell line or insect cells. 

In 1976 Herbert Boyer, one of the discoverers of the rDNA technique and a member of the faculty at UCSF, and Robert Swanson, a venture capitalist with MIT degrees in chemistry and business, formed Genentech. As Swanson put it, in terms reminiscent of those of Landau in chemicals, For Genentech, the strategy from the beginning was to be able to make and sell our own products. Therefore we needed not only to generate products but to manufacture them and build the marketing force to sell them. ... 

These guidelines are concerned with the quality assurance of pharmaceutical and biological products made using recombinant DNA (rDNA) techniques and intended for use in humans. 

It is undesirable to use in production any agent known to provoke sensitivity reactions in certain individuals, such as penicillin or other 8-lactam antibiotics. Many of the general requirements for the quality control of biological products, such as tests for potency, abnormal toxicity, pyrogenicity, stability and sterility, also apply to products made by rDNA techniques. 

Products such as killed vaccines, including those made by rDNA techniques, toxoids and bacterial extracts may after inactivation be dispensed into containers on the same premises as other sterile biological products, providing that adequate decontamination measures are taken after filling, including, if appropriate, sterilization and washing. 

The first successful attempts to tailor a protein hormone for therapy by rDNA techniques has yielded interesting insulin analogues (66,67,68). 

Teriparatide, a polypeptide prepared by rDNA techniques, consists of the first 34 amino acid residues from the N-terminal end of PTH. It has been shown to contain all the structural requirements for the full biological activity of PTH. When teriparatide is administered daily by SC injection, it stimulates osteoblastic activity at the expense of osteoclastic activity, and this... 

The patent office in 1980 acloiowledged that the claims by Cohen and Boyer, for the use of plasmids and restriction nucleases constituted a novel invention of recombinant-DNA technology. Stanford s decision to patent the rDNA technique and the breadths of the claims upheld by the Patent Office were widely noted, and they set patterns, both in academia and in industry [83]. 

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