Cheers J,
The NSCLC target, beta tubulin, is also expressed in the testes and brain.... MK drew a blank when asked about what the off-target effects of beta-tubulin KO are (youtube talk at recent european conference). I hope we can address this before clinical trials begin, though its not MKs priority to do that work. Its ours....
This you might find interesting. In science this week I read a commentary of recently developed mice with humanised livers and the toxicology testing of a failed candidate HBV drug. The link is below. In 1993, five patients (n=15) died of liver failure after receiving a potential HBV drug. Preclinical tests in mice, rats, dogs and primates did not lead to liver failure. This new chimeric mouse with humanised liver does present with the human symptoms.....
www.sciencemagazinedigital.org/sciencemagazine/18_april_2014?sub_id=AXDakcK7AXvD&folio=244#pg20
And here are the pubmed articles relating to these mice
http://www.ncbi.nlm.nih.gov/pubmed/?term=chimeric+TK-NOG+mice+with+humanized+livers.
This could be the way forward for Suhy et al., if the AAV8 doesn't get the desired transfection. Use these mice to determine the best serotype going forward.... Let's do the science in parallel. Forget the crap-shoot... It will take us a year to optimize. We could test 4-5 different serotypes in that time. $200-300K USD max (much cheaper done in the US)....
I'm amazed that there are mice with humanized livers..... And the way these fields are advancing boggles the mind.... The future for BLT is anyone's guess....
Cheers,
MS
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