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- Title
1031. Improved Intranuclear Delivery of PNA-Peptide Conjugates Designed for Chromosomal Gene Targeting.
- Authors
Rogers, Faye A.; Glazer, Peter M.
- Abstract
Peptide nucleic acids (PNAs) are DNA binding molecules, which offer the potential to selectively modulate gene expression. These DNA analogues in which the purine and pyrimidine bases are attached to a polyamine backbone, maintain a spacing similar to DNA, but result in an achiral, neutrally charged molecule. PNAs can bind to DNA via Watson-Crick complementarity, with binding affinities significantly higher than those of the corresponding DNA oligomers. However, the biological activity of these potential antigene compounds has been limited by inefficient cellular uptake. Currently, the techniques used to introduce these molecules into cells, microinjection, co-mixture with cationic lipids, and electroporation, are limited by their cytotoxic effects. Here, we investigate the effect of cell-penetrating peptides on the biological activity of PNAs as measured in an assay for gene-targeted mutagenesis. Using the transport peptide derived from the third helix of the homeodomain of antennapedia (Antp), we tested PNA-peptide conjugates compared to unmodified PNAs. Confocal microscopy studies indicated increased cellular uptake of PNA when linked to Antp, consistent with the gene targeting data. Furthermore, i.p. injection of labeled PNA-Antp conjugate indicate in vivo nuclear uptake in mouse tissue. These results suggest that peptide conjugation may enhance intranuclear delivery of reagents designed to bind to chromosomal DNA, thus improving antigene potential.Molecular Therapy (2006) 13, S396–S396; doi: 10.1016/j.ymthe.2006.08.1126
- Subjects
NUCLEIC acids; PEPTIDES; GENE targeting; GENE expression; PURINES; PYRIMIDINES
- Publication
Molecular Therapy, 2006, Vol 13, pS396
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.1126