Intraductal AAV Delivery
Overview
Intraductal AAV delivery is a surgical technique in which adeno-associated virus (AAV) vector preparations are injected directly into the mammary ductal tree through the nipple orifice, enabling targeted transduction of luminal epithelial cells lining the ducts. The approach exploits the anatomy of the mammary gland to achieve cell-type-selective gene delivery or genome editing without systemic exposure or surgical dissection. When combined with CRISPR-Cas9 (in Cas9-transgenic animals), intraductal AAV delivery enables somatic engineering of specific oncogenic mutations in the mammary epithelium to generate tumor models.
Used by
- Intraductal injection of AAV2/9 carrying CRISPR guide RNAs (and HDR donor for Pik3caH1047R) into Cas9-transgenic rats was used to model six breast cancer genotypes; AAV-NT (Nf1+Tp53 dual gRNA, 2×10^10 gc/gland) produced tumors in 100% of rats within one month; AAV-PNT (triple-edit Pik3ca/Nf1/Tp53) reached 8-day median latency. PMID:26437033
Notes
- Typical injection volume: ~50–100 µL per gland, delivered through the nipple under isoflurane anesthesia.
- Cell-type selectivity: luminal epithelial cells (~25–30% of total mammary cells) are preferentially transduced; estimated editing rate in luminal cells is 2–3× higher than the whole-gland allelic rate.
- Serotype AAV2/9 used in the rat mammary gland studies cited here; other serotypes may be used for different target tissues.
- The same technique applied to mice produces ER-/PR- metaplastic tumors even with identical CRISPR constructs, illustrating species-specific lineage determinism.
Sources
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