AAV9-MT9

AAV9-MT9 is an adeno-associated virus serotype 9 (AAV9) gene therapy candidate designed for the treatment of Tuberous Sclerosis Complex type 2 (TSC2). Developed by researchers at Nationwide Children's Hospital in collaboration with BridgeBio, the therapy utilizes a rationally designed micro-Tuberin (MT9) transgene. Because the full-length TSC2 gene exceeds the standard AAV packaging limit, MT9 was engineered using AI-guided protein structure prediction (AlphaFold 2) to include only the essential structured domains and functional motifs of the Tuberin protein while excising unstructured regions. The mechanism of action involves restoring the TSC complex's ability to negatively regulate the mTORC1 signaling pathway, which is chronically overactive in TSC2 patients. Preclinical data in mouse models have demonstrated that AAV9-MT9 can significantly extend survival, reduce seizure frequency, and improve motor function, providing a potential long-lasting intervention for the neurological complications of TSC2.

Other names

micro-Tuberin 9micro-Tuberin9micro-Tuberin-9AAV9-micro-TuberinAAV-9-micro-TuberinAAV 9-micro-Tuberin