Viral vectors manufacture

Viral vector manufacture for therapeutic purposes involves initial viral propagation in appropriate animal cell lines, viral recovery, concentration, purification and formulation. A generalized manufacturing scenario for adenoviral-based vectors is outlined in Figure 14.7. The manufacture of alternative viral vectors likely follows a substantially similar approach. 

Master and working banks of both the viral vector and the animal cell line will have been constructed during the drug development process (see Chapter 4). Manufacture of a batch of vector, therefore, will be initiated by the culture of packing cells in suitable animal cell bioreactors. The... 

Product manufacture entails viral vector propagation in a suitable animal packing cell line (known as HEK 293). After cell recovery and lysis, the crude product is clarified by filtration and concentrated by ultrafiltration. The product is then treated with a nuclease preparation in order to degrade contaminant DNA and further downstream processing entails multi-step high-resolution column chromatography (see also Figure 14.7). 

The alternative approach is to use non-viral vectors, such lipid-based, peptide-based and polymer-based delivery systems, as described in detail in Chapter 14. Liposomes are relatively easy to manufacture, are generally non-toxic and are devoid of the capability to cause an infection (see Section 5.3.1). However, a number of limitations are associated with their use. For example, it is difficult to direct liposomes to a particular type of cell. Liposome/DNA complexes which may be internalized by the target cells are... 

Among non-viral vectors, the lipoplex and polyplex systems [69,70], in which cationic Hpids and polycations, respectively, associate with DNA through an electrostatic interaction, are most widely studied for both in vitro and in vivo transfection. Their assets are that they can carry various size ranges of DNA, ease in manufacturing and mass production, a variety of chemical designs with smart fimctions, and their surface properties can be readily controlled by changing the charge ratio between the cationic polymer and DNA. 

Pharmaceutical Applications Viral Vectors, Plasmid and Vaccine Manufacturing Processes... 

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