This is a very interesting article. Take note of the section re...

This is a very interesting article. Take note of the section re the liver target and the endosome escape. Also take note of the reference to the Asialoglycoprotein receptor and the GalNac cargo in the article.

https://www.chemistryworld.com/news/breaking-the-silence-of-rna-interference-drugs/3009784.article 

One of the major challenges with the siRNA cargo class is how to safely deliver these molecules directly into the cytoplasm of specific cells and getting them out of the endosome. And this is where lipid nanoparticles could potentially come into play to address this challenge. Phylogica's platform using their FPPs for cell specific delivery with siRNA cargoes could potentially open up vast therapeutic opportunities.

Note, what was highlighted in the company update dated 17 January 2019.

"Read-outs will be delivered across the three cargo classes highlighted for prioritisation in the annual report (see ASX announcement of 15 October 2018 for more detail). In addition to the milestones described above for our priority ‘in-house’ cargo classes, we will also pursue partnerships with leading global commercial and academic groups to advance a range of alternative cargo classes in 2019. These partnerships will allow us to progress work in three additional classes of cargo (scaffolds, protein degradation and small interfering RNA) through to ‘proof-of-concept’ milestones without impacting on our internal focus of pushing towards clinical evaluation of our ‘in-house’ pipeline."

https://hotcopper.com.au/threads/ann-ceo-letter-and-operational-update.4606263/?post_id=37138911 

A recap of what I took note of in the announcement dated 17 January 2019.

* Page two in the announcement highlighted a diagram with targeted delivery in the liver.
* The GalNac cargo was what bound to the Asialoglycoprotein receptor and as a result increased its potency and delivery into the liver cell by 30-60 fold.
* It improved the uptake of cargo over conventional CPPs.
* It was able to do so more efficiently directly into the cell type of interest i.e., the liver cell.

Note: * PYC's second generation peptides are able to deliver 25-150 times (in vitro) as much cargo into a target cell compared to a cargo alone. How effective will their technology be? For that we'll have to wait and see.

Tony