Regarding the two macaques that developed anti-LL antibodies only to later develop detectable LL and achieve RO via AAV…why not dose the current form of LL weekly, upon receiving the AAV treatment, while the myocytes get to the point where they are cranking out sufficient amounts of LL? The timing on this will need to be worked out but if it leads to a functional cure, it may be worth pusueing.

Of course, there is work to be done to determine why these two didn’t take to the AAV like the other two successfully that did, but it seems to me that overwhelming the body with Sub-q LL might be worth a shot while the AAV takes hold.

Could it be that AAV produced only low levels of LL and therefore suboptimal RO which allowed for the immune system to develop anti-LL antibodies? And when the AAV finally got cranking, full RO and LL levels were too much for the anti-LL antibodies?