Through transcriptional activation, saRNA therapeutics promise a revolution in our ability to modulate previously undruggable targets.
saRNA is loaded onto Argonaute proteins (Ago) in the cytosol and the active complex translocates into the nucleus.
Inside the nucleus the Ago complex associates with either promoter elements of the target gene or natural antisense transcripts which serve as a docking site.
By recruiting endogenous transcription complexes, including RNA Polymerase II (Pol-II), the Ago complex activates the gene’s transcription of messenger RNA (mRNA).
The new mRNA is naturally processed into protein. MiNA has demonstrated the therapeutic potential of up-regulating several proteins in a diverse range of pre-clinical models.
saRNAs are small oligonucleotide drugs, similar in chemical structure to siRNAs. As a consequence saRNA drug development benefits from the use of established medicinal chemistry and drug delivery, resulting in accelerated pharmaceutical development cycles.
MiNA has developed a powerful bioinformatics platform to design saRNA for targeted gene activation. saRNA sequences recognise elements upstream of the mRNA transcription initiation site and downstream of the polyA site. Furthermore the platform does not rely on specific knowledge of noncoding RNA complexity at the target gene.