Karmaswimswami, a liver specialist Dr, has been posting some...

Karmaswimswami, a liver specialist Dr, has been posting some great posts on Gumshoe about Benitec, a US forum.

http://www.stockgumshoe.com/reviews/biotech-supertrader/this-tiny-unknown-biotech-is-about-to-unleash-its-holy-grail-drug/#comment

I'd like to invite you to join here and post here as well. As a Dr myself, I particularly liked your refutation of the recent Kay et al paper that Dirk gleefully posted to put down Benitec. I admit, the Kay paper worried me a little but KSS's refutation has given me much more confidence. An extract of KSS's post follows:

"In mice with chimeric livers, there is histologic chaos as regards the newly-deposited human hepatocytes. Rappaport zone architecture, sinusoidal architecture, the formation of gap junctions between hepatocytes, and likely the migration of macrophages and lymphocytes….all of these things are distorted and non-native. This leads me to assert that Lisowski and Kay’s conclusion that, based on this system, AAV8 is a poor transducer of human hepatocytes, is nothing if not disingenuous. Our understanding of how AAV8 gets into hepatocytes is incomplete, of course, but to argue based on a system where perfusion, juxtaposition to endothelium, and access to non-hepatocyte liver cells is perturbed that AAV8 is ineffective is just not sound science. Theirs is but one observation, an incomplete one, and one based on a highly imperfect model system. Its broader interpretability as to AAV8 efficacy in human patients is utterly indeterminate. In their system, AAV8 may be having at mouse hepatocytes more readily than human ones because the native mouse hepatocytes remain in a setting of normal perfusion and adjacency to endothelial and sinusoidal lining cells. The same absolutely cannot be said of the human hepatocytes in this system."

I'll attempt to simplify this for the non medical readers:

Kay's group said that AAV8, the virus ddRNAi inserter we are using in the upcoming Hep C trial, doesn't actually get into human liver cells very well. But the model they used was a mouse liver that had human liver cells put into it. KSS argues very well that the process that puts the human liver cells in to the mouse liver totally changes the way the liver works and that it is very possible that AAV8 doesn't seem to get in because they have busted the liver and a busted liver doesn't take up the AAV8. This should not happen with the normal human livers we are treating in the upcoming trial.