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rAAV-Notch1D
- Development stage
- Preclinical
- Lead developer
- Louisiana State University Health Sciences Center
- Modality
- Viral Vectors → Gene Addition/Replacement → Gene Therapies
- Administration
- Intratumoral
01
Overview
rAAV-Notch1D is an experimental gene therapy consisting of a recombinant adeno-associated virus (rAAV) vector that encodes a soluble Notch1 decoy (Notch1D). It is specifically designed to treat triple-negative breast cancer (TNBC) by blocking the Notch signaling pathway within the tumor microenvironment. Unlike systemic Notch inhibitors such as gamma-secretase inhibitors (GSIs), which often cause intestinal and immune toxicity, rAAV-Notch1D is administered intratumorally to provide localized inhibition. The construct features a C1QTNF3-derived collagen domain (CD) to facilitate the trimerization and stabilization of the secreted decoy protein. Preclinical studies indicate that rAAV-Notch1D reduces cancer stem cell populations, inhibits tumor growth, and enhances the activity of immune checkpoint inhibitors like anti-PD1 by increasing tumor-infiltrating lymphocytes (CD3+ and CD8+ cells).
- Other names
- recombinant adeno-associated virus encoding a soluble Notch1 decoyrAAV-Notch1 decoyrAAV-Notch-1 decoyrAAV-Notch 1 decoy
02
Targets
NOTCH (Neurogenic locus notch homolog protein 3)
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