Synthesis of Peptide Nucleic Acid (PNA) and Entrapment of PNA into Liposomes

Abstract

Peptide Nucleic Acid (PNA) is a synthetic pseudopeptide nucleic acid analogue in which the deoxyribose phosphodiester backbone of DNA is replaced by a pseudo-peptide composed of N-(2 aminoethyl)glycine units, resulting in an achiral and uncharged DNA mimic. PNA is chemically stable and resistant to enzymatic cleavage
and with high binding affinity and specificity to nucleic acids. Therefore PNAs are very strong candidates as effective antisense or antigene agents. They have shown both
antigene and antisense activities against target genes and transcripts, respectively. PNAs
are also very useful biomolecular tools.

Unfortunately, for certain applications of PNA, there are some severe drawbacks such as its poor water solubility and poor cellular uptake. Fast progress in the exploration of PNA as an experimental and therapeutic regulator of gene expression has been hampered by these drawbacks.

Several transfection protocols for PNA have now been studied, such as microinjection, electroporation and co-transfection with DNA. Among the different delivery strategies,
liposomes are a potential way to delivery PNA into cells since liposomes can protect various molecules from the external medium and can deliver molecules directly into cells. Moreover, it is also possible to specifically target liposomes by coupling proteins
or antibodies to their surface.

In this project PNA oligomers were synthesized and labeled with fluorescein. These oligomers were entrapped into the liposome and from the results, we can draw a
conclusion that the method of dehydration-rehydration is encouraging method for the
preparation of PNA-liposomal delivery systems which can offer high PNA loading, mild preparation methods and the potential to optimise PNA release.

Date of Award	Sept 2004
Original language	English
Awarding Institution	Aston University