I gather you are referring to Spark's HemoB program and based on what I can see on clinical trials.gov and their website (see below), it will be IV administration of the AAV w/ steroid administration and other measures to mitigate against the immune response, consistent with what Dr. High mentioned they'd learned from earlier trials.
I believe SGMO also mentioned steroid administration in their RAC HemoB meeting (please don't quote me on that, I'd have to go back and watch the SGMO RAC meeting video again), which I presume is included as a standard measure now when administering liver-trophic AAV via IV to mitigate against a heightened immune response.
Also assuming these measures aren't going to totally blunt (i.e, totally negate) the immune response that can result in T cell-mediated destruction of hepatocytes that have been transduced by the AAV (
more on that here).
So long story short, in such a case, I much prefer the premise behind SGMO's approach where the aim will be to achieve albumin locus safe harbor site-specific integration of the FIX transgene to mitigate against loss of expression for hepatocytes transduced by AAV. The premise, as least as far as I can see, being those hepatocytes that ultimately survive an immune response w/ SGMO's FIX transgene integration approach, then have the opportunity to subsequently undergo mitosis & proliferate.
As I recall, Dr. High noted that eventually the steroids can be tapered down which I took to mean the T-cell mounted response to hepatocytes transduced with liver-trophic AAV's isn't something they observed to be chronic and extremely long-lived immune response.
As always, if someone sees a flaw in my logic for what I have in italics above or they see a number of things I haven't considered or have overlooked, please feel free to weigh in.
...The SPK-FIX program builds on our team’s previous Phase 1 clinical trials which demonstrated initial proof-of-concept in using gene therapy to deliver and express a therapeutic gene in the liver. In December 2014, we entered into a global collaboration with Pfizer for the development and commercialization of product candidates in our SPK-FIX program. With Pfizer we are developing novel bio-engineered AAV vectors utilizing a high-activity factor IX transgene and a treatment protocol designed to mitigate immune responses seen in other hemophilia B gene therapy trials, including our own, that have limited the duration of efficacy. We initiated a Phase 1/2 trial in June of 2015.