Association with viral protein

The latter studies on pDNA delivery of a therapeutic gene to treat metabolic diseases, autoimmune diseases, viral infections or cancer suggest that naked pDNA could be used for gene delivery. The advantages of this type of therapy include the simplicity of i.m. injection, the requirement for only a limited number of i.m. injections to achieve measurable serum levels of the therapeutic protein, the maintenance of stable serum levels of the protein thereby avoiding side-effects associated with bolus protein delivery and the avoidance of the use of viral vectors which pose safety concerns and which can induce anti-vector antibodies. With improvements in pDNA design and delivery, this type of gene therapy may someday prove useful for therapy of a variety of human diseases. 

Furthermore, CVB3 likely utilizes the UPS to modify its viral proteins for its replication, as CVB3 RNA-dependent RNA polymerase 3D is either directly ubiq-uitinated or associated with ubiquitinated proteins in infected cells (unpublished results). 

On the other hand non-viral vectors, which have only been used for the past two decades, have yet to become a marketing reality because they still do not meet adequate safety profiles, the standards for efficient delivery, or the rigorous testing of clinical trials. Non-viral vectors involving cationic liposomes have been most widely used in pre-clinical and clinical trials however, apart from the non-viral delivery of genetic material, which is inefficient when compared to the delivery associated with viral vectors, non-viral vectors stiU suffer from some of the same toxicity issues from which viral vectors suffer. Some of the delivery issues such as hpoplex instability in the blood stream, interaction with plasma proteins, and non-specific cellular interactions persist, despite the extensive investigations and corrective maneuvers that have been conducted over the past decade. Therefore, currently, the only advantage with cationic lipids seems to be their inability to transform host cells into cancerous cells (3,4). 

Baglioni, C., Lenz, J. R., Maroney, P. A., and Weber, L. A., 1978, Effect of double-stranded RNA associated with viral mRNA on in vitro protein synthesis, Biochemistry 17 3257. 

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