RNA therapeutics built on latest generation PMOs (Phosphorodiamidate morpholino oligomers)
- RNA is the molecular code your cells use to transcribe the genetic code in your DNA, process that information, and translate it into proteins.
- RNA therapeutics alter the way RNA is processed, and hence how genetic messages are translated to proteins, to alter disease processes.
- PMOs are synthetic chemical structures modelled on RNA. PMOs are a type of Antisense Oligomer, and function similarly to Antisense Oligonucleotides (ASOs).
- PMOs and ASO both contain nucleic bases which bind the complementary strand of RNA to have an effect on how the cell will process that target RNA strand.
- PMOs can be designed to have many effects on the target RNA, including:
- Alternative splicing
This approach is used to up- or down-regulate the production of proteins, or to alter the function of the protein by changing the splicing.
- Modulating and stabilising mRNA
PMOs can help to modulate and stabilise pre-mRNA splicing. This process prevents naturally occurring non-productive alternative splicing and promotes the generation of productive mRNA.
- Translation suppression
PMOs can prevent the cellular machinery from translating mRNA into a protein. As a result, the PMO inhibits translation of an undesirable protein or viral DNA.
- Alternative splicing
- RNA PMO’s are clinically and commercially validated molecules. The first approved PMO for the treatment of Duchene muscular dystrophy, Exondys51, was co-invented by our Chief Scientific Officer, Professor Sue Fletcher.
Revolutionary peptide delivery technology
While PMOs and other RNA therapeutics, including ASOs and siRNAs, have shown early promise, efficient delivery of these therapies to cells remains the single largest barrier for the technology.
- Cell-penetrating peptides (CPPs) are a clinically validated solution to this problem.
- Peptides are short chains of amino acids which due to their sequence and properties can deliver drugs safely and effectively across a cell membrane.
- We leverage our proprietary libraries – constructed out of the genomes of bacteria, viruses, and archaea – to identify the optimal sequences designed by these organisms to safely enter human cells.
- Using our CPP platform technology, we have identified a CPP for our lead drug program VP-001, to deliver a PMO to the very back of the retina in an eye.
- We are developing next-generation PPMO-based (Peptide-PMO) chemistries for advanced RNA-targeted therapeutics. Our PPMO-based chemistries are designed to enhance tissue targeting, delivery into the cell, safety and drug potency.