Novel chemistry could yield improved antisense
acids - a promising drug category that has been limited to date by
an expensive and cumbersome synthetic process.
Peptide nucleic acids (PNAs) mimic DNA and bind to complementary DNA or RNA sequences. They can be used as 'antisense' therapeutics, shutting off the expression of specific proteins in the cell. But to date the high cost of synthesis has limited their use to laboratory tools, despite potential advantages over other sequence specific compounds such as antisense oligonucleotides.
In PNAs, the entire phosphate sugar backbone of the sequence is replaced by an uncharged polyamide backbone with the side groups, purine and pyrimidine bases, found in biological nucleic acids.
Compared to antisense oligonucleotides PNAs are extremely stable and are more specific in their action, reducing the risk that they might bind to and affect other protein syntheses which could lead to side effects.
Moreover, preliminary reports suggest that the PNA sequences could act as a template for cellular production of specific proteins, something which is not achievable with the current generation of antisense oligos. This suggests that PNAs could effectively be used to 'deliver' active peptide drugs directly into the cell.
And in common with the much-lauded RNA interference (RNAi) technology - also used as a lab tool at present but considered to have significant potential in therapy - PNAs can achieve this silencing with very short sequences. RNAi involves the use of short lengths of double-stranded RNA to switch off gene function.
Panagene's novel peptide nucleic acid chemistry can be used to make PNA monomers - the building blocks of PNA compounds - at a large scale and at low cost, claims the company. It can also synthesise chains of PNA monomers into oligomers at high purity.
Dr Sungkee Kim, CEO of Panagene, said that the new PNA chemistry "makes parallel and large scale synthesis of oligomers possible."
This means that PNAs for use in high throughput functional genomics, molecular diagnostics, microarray chips, and as antisense therapies are now available at an affordable cost.
"This new cost-efficient manufacturing technology of PNA oligomers is specially practical for antisense application where production scale and manufacturing cost of drug material is the first priority of consideration," he commented.
Panagene presented this new PNA chemistry for the first time at the recent TIDES 2004 nucleotide and peptide conference, in Las Vegas, US, for which it was selected to receive best poster award.
The company is now looking for strategic partners which can help it exploit the new PNA chemistry.
