Comparison of novel delivery systems for antisense peptide nucleic acids.
J Control Release
; 109(1-3): 24-36, 2005 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-16290244
ABSTRACT
Peptide nucleic acids (PNAs) provide a powerful tool to study the mechanism of transcription and translation, an innovative strategy to regulate target gene expression. They have been successfully used in antisense technology, for their ability to specifically bind to messenger RNA (mRNA) targets and to inhibit translation of the target genes. However, unlike most of the DNA and RNA oligonucleotides, PNAs are poorly penetrated through the cell membrane, partially due to their uncharged property. To enhance the efficiency in PNA delivery, many strategies have been explored. We here compare the efficacy of three different delivery strategies for antisense PNA 1) conjugation to hydrophobic peptides, 2) adsorption onto polymeric microspheres and 3) encapsulation in autologous erythrocytes. To this purpose, we designed and prepared PNA sequences able to inhibit the expression of macrophage enzymes involved in inflammatory process, i.e. nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) and tested their antisense activity in a murine macrophage cellular model. Both delivery through polymeric microspheres and encapsulation into erythrocytes allowed the antisense activity of unmodified PNAs at nanomolar concentration.
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Base de dados:
MEDLINE
Assunto principal:
Elementos Antissenso (Genética)
/
Sistemas de Liberação de Medicamentos
/
Ácidos Nucleicos Peptídicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article