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Vector Design for Improved DNA Vaccine Efficacy, Safety and Production.

Williams JA - Vaccines (Basel) (2013)

Bottom Line: Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery.These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes.Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy.

View Article: PubMed Central - PubMed

Affiliation: Nature Technology Corporation/Suite 103, 4701 Innovation Drive, Lincoln, NE 68521, USA. jim@natx.com.

ABSTRACT
DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy.

No MeSH data available.


Related in: MedlinePlus

(a) DNA vaccine vector production and application flowchart. Stages 1 and 4 are very sensitive to vector changes and must be optimized coordinately since vector modification to enhance one parameter can have multiple undesired effects on other parameters. Stages 2 and 3 are largely generic; (b) Insert design flowchart.
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vaccines-01-00225-f001: (a) DNA vaccine vector production and application flowchart. Stages 1 and 4 are very sensitive to vector changes and must be optimized coordinately since vector modification to enhance one parameter can have multiple undesired effects on other parameters. Stages 2 and 3 are largely generic; (b) Insert design flowchart.

Mentions: The transcribed 3' and 5' untranslated regions (UTRs) flanking the transgene should not contain open reading frames (ORFs) since ORFs in these regions have been shown to be translated into immunogenic peptides [16]. The bacterial region combines a high copy replication origin, most usually the pUC origin, with a selectable marker. Perhaps surprisingly, certain orientations and compositions of bacterial region sequences can dramatically reduce eukaryotic region directed transgene expression, manufacturing yields, and plasmid quality in the E. coli host [17,18]. Reduced expression with certain backbones may in part be due to production, from cryptic promoters in the vector backbone, of double stranded RNA (dsRNA) that triggers protein kinase R (PKR) mediated translational shutdown or RNA interference [19,20]. Thus, since both bacterial production and expression in the target organism are very sensitive to vector changes (Figure 1a), a critical part of vector design is careful selection and assembly of bacterial region selection and replication sequences.


Vector Design for Improved DNA Vaccine Efficacy, Safety and Production.

Williams JA - Vaccines (Basel) (2013)

(a) DNA vaccine vector production and application flowchart. Stages 1 and 4 are very sensitive to vector changes and must be optimized coordinately since vector modification to enhance one parameter can have multiple undesired effects on other parameters. Stages 2 and 3 are largely generic; (b) Insert design flowchart.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494225&req=5

vaccines-01-00225-f001: (a) DNA vaccine vector production and application flowchart. Stages 1 and 4 are very sensitive to vector changes and must be optimized coordinately since vector modification to enhance one parameter can have multiple undesired effects on other parameters. Stages 2 and 3 are largely generic; (b) Insert design flowchart.
Mentions: The transcribed 3' and 5' untranslated regions (UTRs) flanking the transgene should not contain open reading frames (ORFs) since ORFs in these regions have been shown to be translated into immunogenic peptides [16]. The bacterial region combines a high copy replication origin, most usually the pUC origin, with a selectable marker. Perhaps surprisingly, certain orientations and compositions of bacterial region sequences can dramatically reduce eukaryotic region directed transgene expression, manufacturing yields, and plasmid quality in the E. coli host [17,18]. Reduced expression with certain backbones may in part be due to production, from cryptic promoters in the vector backbone, of double stranded RNA (dsRNA) that triggers protein kinase R (PKR) mediated translational shutdown or RNA interference [19,20]. Thus, since both bacterial production and expression in the target organism are very sensitive to vector changes (Figure 1a), a critical part of vector design is careful selection and assembly of bacterial region selection and replication sequences.

Bottom Line: Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery.These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes.Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy.

View Article: PubMed Central - PubMed

Affiliation: Nature Technology Corporation/Suite 103, 4701 Innovation Drive, Lincoln, NE 68521, USA. jim@natx.com.

ABSTRACT
DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy.

No MeSH data available.


Related in: MedlinePlus