VGX Pharmaceuticals LLC

Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge with pathogenic SIVmac251. Two groups of macaques were vaccinated with DNA plasmids producing different antigen forms, “native” and “modified,” inducing distinct immune responses. Both groups showed significantly lower viremia during the acute phase of infection, whereas the group immunized with the native antigens showed better protection during the chronic phase (1.7 log decrease in virus load, P = 0.009). Both groups developed strong cellular and humoral responses against the DNA vaccine antigens, which included Gag, Pol, Env, Nef, and Tat. Vaccination induced both central memory and effector memory T cells that were maintained at the day of challenge, suggesting the potential for rapid mobilization upon virus challenge. The group receiving the native antigens developed higher and more durable anti-Env antibodies, including neutralizing antibodies at the day of challenge. These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model.

Many recent studies have addressed the impact of gene patents and methods of gene delivery on downstream research and innovation. The field of gene therapy has progressed over the last 10 years due to the rapid advancement in delivery technology. Efficient delivery of genes into target cells depends on the absence of cell injury, oncogenic mutation or inflammation. Gene transfer technology saw a significant boost by the applications of in vivo electroporation. This approach is versatile and safe and can be used to deliver nucleic acid fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues, such as skeletal muscle, skin and liver. Many have applied this approach in autoimmune or inflammatory diseases, for the intratumoral delivery of therapeutic vectors, or for systemic delivery of endocrine hormones, hematopoietic factors, antibodies, enzymes, or numerous other protein drugs. This technique has been found to strongly boost DNA vaccination against infectious agents or tumor antigens. in vivo Electroporation has been performed in humans. This review will focus on the intellectual property revolving around recent developments in the area of electroporation, including devices and methodology for various applications.

Previous studies showed that when growth hormone-releasing hormone (GHRH) was administered to either pregnant rats or pigs as a plasmid-mediated therapy, pituitary weight, somatotroph and lactotroph numbers, and postnatal growth rate of the offspring increased. To determine if these responses resulted from direct effects of GHRH on the fetus or were secondary to effects incurred in the mother, we studied in the rat the transplacental transfer of a GHRH analog (HV-GHRH) to the fetus from the maternal circulation. For the in vivo study, HV-GHRH was labeled with 125I and purified by reverse-phase high-performance liquid chromatography (HPLC). At 18 days of gestation, pregnant dams were administered a priming intravenous dose followed by a constant infusion of the labeled peptide. Approximately 2 days later, intact [125I]-HV-GHRH was isolated from the fetal liver, stomach contents, and brain. The amounts of tracer were positively correlated with those present in the corresponding dam's plasma. These data suggest that a GHRH analog of nonplacental origin, even at physiologic concentrations, can cross the placenta and, therefore, has the potential to influence fetal pituitary development directly.