Molecular Delivery of Plasmids for Genetic Vaccination

Abstract

Plasmid vaccination is a smart gene delivery application mostly achieved through the utilisation of viral or copolymeric systems as surrogated carriers in micro or nano formulations. A common polymeric protocol for plasmid vaccine formulation, which as somewhat been successful, is via the complexation of the DNA molecules with a cationic polymer, and encapsulating in a vehicular carrier polymer. Even though plasmid vaccination research has not witnessed the much anticipated success, due a number of cellular and physicochemical reasons, application of copolymeric carriers with tight functionalities is a promising strategy to optimally deliver the DNA molecules; in view of the available chemistries and physical properties that could be tuned to enable enhanced targeted delivery, uptake and specific transfection. This also enables the targeting of specific epitopes and antigen presenting cells for the treatment of many pathogenic infections and cancer. This paper provides a brief critical review of the current state of plasmid vaccines formulation and molecular delivery with analysis of performance data obtained from clinical trials.

Live-cell imaging to compare the transfection and gene silencing efficiency of calcium phosphate nanoparticles and a liposomal transfection agent

“…1, 2, 3, 4, 5, 6, 7, 8, 9, 10 As nucleic acids alone are not able to penetrate the cell membrane, they must be transported with a suitable carrier. 11 Different strategies have been developed to address this problem, ranging from physical methods like electroporation 12 over viral transduction 13 to various kinds of nanosystems.…”

“…3, 5, 6, 7, 11, 14, 15, 16, 17 Typical nanoparticles for transfection comprise gold, 18, 19, 20 iron oxide, 21 silica, 22 carbon nanotubes 23 and many different polymers. 2, 24, 25 …”

Cationic Nanostructures for Vaccines Design

“…This model study emphasized the importance of well-defined chain length for cationic polymers in DNA vaccines; this type of cationic polymer poly (2-aminoethyl methacrylate) was also recently reviewed for exploring structure–function relationship while delivering DNA [ 174 ]. Excellent reviews are available on micro- and nanoparticles for DNA vaccine delivery [ 175 ] and on molecular delivery of plasmids for genetic vaccination [ 176 ].…”

Nanoengineering of vaccines using natural polysaccharides

“…Moreover, nucleic acids can be tailored to express antigens that are chemically or structurally different from their native form, with the intention of improving their immunogenicity (Alpar et al, 2005;Deering et al, 2014;Kramps and Probst, 2013). The main limitation of this approach is the low level of gene expression achieved upon administration, a limitation that can be overcome by designing effective viral and non-viral transfection vectors (Alpar et al, 2005;Mazid et al, 2013).…”

“…Plasmid DNA vaccination, based on the administration of selected antigen-encoding DNA through a plasmid vector, has been applied to prevent diseases such as malaria and HIV and also as a therapeutic approach in cancer immunotherapy. Some of these formulations have already reached the clinical development phase, as recently reviewed by Mazid et al (Liu, 2003;Mazid et al, 2013). Nevertheless, the risk of genome integration and long-term effects of these vaccines are yet to be clarified (Schalk et al, 2006).…”