I was reminded of this comment exchange from last May: https://news.ycombinator.com/item?id=40439379#40440171. TIL that, according to this paper, antisense treatment in the brain has some drawbacks:

> Treatment of mice with antisense oligonucleotides (ASOs) targeting the Prnp transcript decreases expression of PrP and extends the survival of mice previously infected with misfolded PrP (6); however, the limited efficacy of ASOs and the requirement for chronic intrathecal dosing highlight the need for a more potent therapy.