Post by Philipp Beck

In early formulation development for #AAV, it’s tempting to rely on quick biophysical readouts (nanoDSF, DLS, Tagg, vg/capsid titers, ejected DNA) to flag instability. ➡️But what if the vector looks fine by all these methods, yet has no 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧𝐚𝐥 𝐩𝐨𝐭𝐞𝐧𝐜𝐲 after just one day at 40°C? A recent paper by Carina Rodenstein, Dr. Eva Schmid, Natalia Marcova, Andreas Seidl (Leukocare AG + Malvern Panalytical) explores genome release (SYBR Gold), protein unfolding (nanoDSF), and aggregation (SEC-UV) as potential stability indicators, all without functional validation. ☹️ Here is the free-access link: https://lnkd.in/dXqS_Azc 🔎They did attempt a laser force cytology (LFC) assay (Figure 9), but it failed to detect AAV infectivity, with even positive control cells showing no infection. (Could you take this at face value and say: there was no infection? Definitely possible!) While others might view this as a weakness of the report , I'd rather say that this is an honest reminder that functional assays for AAV aren’t exactly plug-and-play. So: when do you bring cell-based potency into #formulation work?