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Summary Electroporation (EP) has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids for gene therapeutic applications. Skeletal muscle is a preferable target tissue for a number of reasons including long-term secretion of therapeutic proteins for systemic distribution and promotion of strong humoral and cellular immune responses post-vaccination. All of these DNA-mediated applications are significantly improved by in vivo EP. We have demonstrated previously that constant-current EP is effective for intramuscular plasmid delivery in mammals and does not cause permanent damage to cells. Numerous other factors impact plasmid uptake and expression after intramuscular injection followed by EP, such as plasmid size, formulation, concentration, injection volume, intensity of the electric field, target muscle, and species and age of the treated subject. These improvements in the conditions of EP can increase the efficacy of plasmid transfer and lower the total amount of plasmid and DNA vaccines required to generate targeted levels of biologically active proteins or antibodies.

Dr. Ruxandra Draghia-Akli et. al.

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Next Article: The kinase activity of c-Abl is known to be tightly regulated. Mechanisms of c-Abl kinase regulation can be classified as intramolecular or intermolecular interactions. Crystallization of the amino (N)-terminal region of c-Abl has revealed that intramolecular folding of the N terminus onto the kinase domain represses intrinsic kinase activity. With regard to intermolecular interactions, recent studies suggested that trans-acting molecules bind to a proline-rich (PR) regions in the carboxyl (C)-terminal portion of c-Abl and activate the kinase. In this review, we focus on c-Abl kinase activation and the mechanisms of substrate phosphorylation mediated by adaptor molecules which bind to the C-terminal PR regions of c-Abl kinase.
The Publication:
Summary Electroporation (EP) has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids for gene therapeutic applications. Skeletal muscle is a preferable target tissue for a number of reasons including long-term secretion of therapeutic proteins for systemic distribution and promotion of strong humoral and cellular immune responses post-vaccination. All of these DNA-mediated applications are significantly improved by in vivo EP. We have demonstrated previously that constant-current EP is effective for intramuscular plasmid delivery in mammals and does not cause permanent damage to cells. Numerous other factors impact plasmid uptake and expression after intramuscular injection followed by EP, such as plasmid size, formulation, concentration, injection volume, intensity of the electric field, target muscle, and species and age of the treated subject. These improvements in the conditions of EP can increase the efficacy of plasmid transfer and lower the total amount of plasmid and DNA vaccines required to generate targeted levels of biologically active proteins or antibodies.
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