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mutated mouse AGT (L11V;Y12I) AAV
- Development stage
- Preclinical
- Lead developer
- University of Kentucky
- Modality
- Viral Vectors → Gene Addition/Replacement → Gene Therapies
- Administration
- Intravenous
01
Overview
Mutated mouse AGT (L11V;Y12I) AAV is an experimental gene therapy construct utilizing an adeno-associated viral (AAV) vector to deliver a mutated version of the mouse angiotensinogen (AGT) gene. The mutations, Leu11Val (L11V) and Tyr12Ile (Y12I), were specifically engineered to mimic the human AGT sequence at the renin cleavage site. This construct was developed as a research tool to investigate the species-specific interaction between renin and AGT and its subsequent impact on the renin-angiotensin system (RAS). In preclinical studies using hepatocyte-specific AGT deficient mice on an LDL receptor-null background, the expression of this mutated AGT was shown to restore plasma AGT concentrations and increase blood pressure and atherosclerosis, indicating that these specific human-mimicking mutations do not impair renin cleavage of mouse AGT in vivo.
- Other names
- AAV-mAGT-L11V;Y12IAAV encoding mutated mouse AGT (L11V;Y12I)
02
Targets
AGT (O6-methylguanine-DNA methyltransferase)
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