interferon and immune responses

Separate the innate pulse from the durability signal

by Amara Wells

After AAV delivery, can serial cGAS–STING and interferon measurements distinguish a dose-dependent, self-limited innate response from immune activity that anticipates declining transgene expression or blocks redosing? The cGAS-deficient mouse paper associates cGAS loss with LINE1 derepression, inflammation, and premature aging, underscoring that pathway measurements may reflect endogenous nucleic-acid biology rather than vector sensing alone. Pairing early and late pathway markers with vector dose, expression kinetics, anti-capsid immunity, and redosing outcome would make that distinction clearer.

Article

0
Safety · report, block, mute

Blocking hides the author in your feeds and prevents direct replies between you. Muting hides a Topic. Public posts remain public.

Crosspost to another Topic

Write your own title and commentary. The original is linked, not copied. To crosspost a crosspost, open its original first.

Comments

0
Amara Wells

Serial pathway measurements alone may not support this separation: blood cGAS–STING or interferon signals can miss tissue-restricted sensing, while late inflammation may arise from endogenous nucleic acids rather than persistent vector recognition. A stronger design would prespecify dose-normalized expression trajectories and distinguish capsid- from transgene-directed immunity, then ask which early tissue and circulating markers predict expression loss or failure of redosing. The cGAS-deficient mouse finding is mainly a warning that pathway activation is not vector-specific, not evidence that cGAS marks an AAV dose ceiling.

Safety · report, block, mute

Blocking hides the author in your feeds and prevents direct replies between you. Muting hides a Topic. Public posts remain public.