Journal: Gene

Article Title: Development and Characterization of a First-in-Class Adjustable-Dose Gene Therapy System

doi: 10.1016/j.gene.2024.148500

Figure Lengend Snippet: Physical and pharmacological cryolipolytic methods for downward adjustment of transgene expression in C57BL/6 (cryolipolysis) and B6 Albino (ultrasound lipolysis and suicide gene-mediated apoptosis) mice. (A) Total flux from the target signal before cryolipolytic down titration (Baseline signal: Pre 15-min) and signal following a series of three 15-minute cryolipolytic treatments, compared to background (n=4 animals); ANOVA, p treatment-number-Cryo <0.05, Fisher’s LSD post-hoc test, p crit =0.05; ANOVA, p treatment-number-Background >0.05. (B) IVIS images of two signals, a 2 μg reference injection on the left side of the animal (orange arrow) and a 10 μg injection on the right side of the animal undergoing cryo-mediated down-titration (blue arrow). (C) Percent reduction in the target signal following two-step ultrasonic lipolysis in B6 Albino mice, compared to background signal , relative to pre-adjustment levels (n=5 animals); ANOVA, p treatment-number-Ultrasound <0.05, Fisher’s LSD post-hoc test, p crit =0.05; ANOVA p treatment-number-Background >0.05. (D) IVIS images of the background signal region of interest (red circle) and target signal region of interest (blue circle) before ultrasound down-titration, after one down-titration, and after two down-titrations. (E) Percent reduction in the target signal following pharmacological activation of the iCasp9 suicide gene, compared to percent reduction in background signal following activation of the suicide gene via subcutaneous administration of the AP20187 dimerizer into B6 Albino mice (n=6 animals); ANOVA, p condition <0.05. (F) IVIS images of the background signal region of interest (red circle) and iCasp9 pharmacologically adjustable signal region of interest (blue circle) before and after AP20187 administration. Statistical significance indicated by letters (groups that do not share a letter are significantly different).

Article Snippet: Durability of gene expression following dosing was confirmed by bioluminescence imaging using a Caliper IVIS ® Lumina XRMS Series III (Caliper Life Sciences, Hopkinton, MA, USA) in vivo imaging system.

Techniques: In Vivo, Expressing, Titration, Injection, Activation Assay