Fig. 1: Schematic showing the mouse experimental design for AAVMUSE-mediated gene therapy to treat chronic diseases.
From: AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation
a, b Schematic representations of the genetic configurations for AAVMUSE-ΔhFGF21 and AAVMUSE-ΔmIL-4. AAVMUSE-ΔhFGF21 containing the muscone-responsive vector AAV2/9-pWX126 (ITR-PSV40-MOR215-1-pA-ITR), the concatenated Gαolf and RTP1S expression vector AAV2/9-pWX127 (ITR-PSV40-Gαolf-P2A-RTP1S-pA-ITR), and the ΔhFGF21 inducible expression vector AAV2/9-pWX252 (ITR-PCRE-ΔhFGF21-pA-ITR) were injected into diet-induced NAFLD model mice; AAVMUSE-ΔmIL-4 comprising AAV2/lung-pWX126 and AAV2/6-pWX345 (ITR-PSV40-RTP1S::pA-ΔmIL-4-PCRE-ITR) were injected into OVA-induced allergic asthma model mice. c Detailed schematic for the muscone-induced transgene system (MUSE) design. The binding of muscone to the G-protein-coupled murine olfactory receptor (MOR215-1) triggers an intracellular surge of the second messenger cAMP via olfactory type G protein α subunit (Gαolf)-mediated activation of adenylate cyclase (AC). Then cAMP binds to the regulatory subunits of protein kinase A (PKA), the catalytic subunits of which are translocated into the nucleus, where they phosphorylate the cAMP-responsive binding protein 1 (CREB1), which binds to a synthetic cAMP-responsive promoter (PCRE) to initiate transgene expression (e.g., ΔhFGF21 or ΔmIL-4).
