Implications of Downstream?

[holdencf]

harcerz4 said on YMB

"Bart, ALNY is trying to make it look like ARC-520 is not downstream of the X gene Orf, when in fact it is. What is odd is ALNY states that their drug is downstream from the "most prevalent hotspot." Why?? Because ARWR is at the most prevalent hotspot - which is where you want to be. ALNY is parsing words in a clever way, and nobody noticed this before"

Can anyone comment on this?  Looks to me ARWR is right smack on top of the genome.  What are the implications of "Downstream?

[mudbug021]

www.ncbi.nlm.nih.gov/pubmed/2457861

X-ORF

ALNY is claiming Arrowhead is missing the target (or the heart?) of HBV. The issue is there is no clinical proof of this, however, ALNY makes it appear as a fact. IMHO, just a lot of double talk from the ALNY CEO at this stage. 

Why some people think ALNY is conceding to ARWR is really furthest from the truth. If anything ALNY is claiming ARWR is failing because they are well downstream of the "Hot Spot" of the X-ORF (1550-1600). But as I said, there is no clinical proof of this is as a fact.

Just a bunch of mudslinging and trying to cloud the truth.   

[holdencf]

mud
I don't know what downstream means in terms of genetics.  I get that ALNY is trying to  trash ARWR.  It just looks to me that ARWR has hit the nail on the head whereas ALNY is off center.  Looking for a scientific perspective. 

[Bio Boy Scout]

ALNY is parsing words and they're trying to make it look like their formulation is "better," when in fact, it is not. Read the following article: www.ncbi.nlm.nih.gov/pmc/articles/PMC2927532/ also at bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-10-214 They did a great job of examining "anti-HBV efficacy of siRNA." They selected four of the most promising plasmids, and the most effective one turned out to be B1789. ALNY's chart on p.9 (http://www.alnylam.com/web/assets/ALN-HBV_AASLD_111515.pdf) shows that both ARWR and ALNY are targeting the X protein (the yellow curve at the bottom of the circle). The location ARWR picked is the "hotspot", whereas ALNY picked an area that overlaps downstream on the polymerase. Upstream and downstream doesn't make a difference, what makes a difference is stability, as well as the "hotspot." The peek in frequency at 1789 (where ARWR is at) is where ALNY would like you to think is not important. What's funny is that you can't read the slide any other way but in ARWR's favor (which is why ALNY pulled it from their featured HBV page). The first article cited above proves that B1789 is where you want to be.

Do the research yourself and see what you come up with. ALNY has delayed their HBV program long enough. I think they know it will not work that well.