Enhancing plasmid nuclear import and delivery system: room for improvement (Abstract in rivista)

Type
Label
  • Enhancing plasmid nuclear import and delivery system: room for improvement (Abstract in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1089/hum.2013.2513 (literal)
Alternative label
  • *Fioretti, D.; *Iurescia, S.; Fazio, V. M.; Rinaldi, M. (* first co-authorship) (2013)
    Enhancing plasmid nuclear import and delivery system: room for improvement
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • *Fioretti, D.; *Iurescia, S.; Fazio, V. M.; Rinaldi, M. (* first co-authorship) (literal)
Pagina inizio
  • A62 (literal)
Pagina fine
  • A62 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 24 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#curatori
  • Fioretti, D. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 1 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 12 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Consiglio Nazionale delle Ricerche (CNR); University Campus Bio-Medico - Rome Italy; IRCCS Casa Sollievo Sofferenza (literal)
Titolo
  • Enhancing plasmid nuclear import and delivery system: room for improvement (literal)
Abstract
  • The use of plasmid DNA vectors for gene transfer represents an important platform for clinical applications, notably with DNA vaccination wherein large-scale vaccine production is not easily manageable with other forms of vaccine including recombinant protein, whole tumor cells, or viral vectors. A variety of clinical trials against cancer have provided evidence that DNA vaccines are well tolerated and have an excellent safety profile. Nevertheless there is still a gap between the experimental data and their application in a clinical setting due to low level of antigen expression. DNA vaccines allow incorporating multiple components to activate and direct selected immune effector pathways and are prone to be delivered in many different manner. To achieve more efficient gene expression from plasmid vectors CMV promoter driven, DNA nuclear targeting sequences (DTSs) are introduced to increase the efficiency of nuclear plasmid uptake from cytoplasm. Electrogenetherapy is promising for the treatment of muscle disorders, as well for the systemic secretion of therapeutic proteins, DNA vaccination, immunotherapy and cancer therapy. The inclusion in a DNA vector backbone of a DTS localized in a non-coding region of the SV40 virus sequence is established to increase in vivo expression up to 20-fold using electroporation delivery in muscle tissue. We have used this delivery technique in combination with plasmids containing a tandem repeat of two 72-bp DNA elements from the SV40 enhancer in preclinical immunization protocols. To evaluate the increase in performance we analyzed over time the IL-2 expression of anti-idiotypic DNA vaccines, developed against an aggressive murine B-cell lymphoma model and co-expressing IL-2 as immunomodulating agent. The antiidiotypic humoral response was assayed as well. Our in vivo results show that the combination of electroporation and a plasmid vector carrying DTSs elements results in efficacious DNA vaccines. (literal)
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