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Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin

Sci Adv. 2021-01;

Pike-See Cheah, Shilpa Prabhakar, David Yellen, Roberta L Beauchamp, Xuan Zhang, Shingo Kasamatsu, Roderick T Bronson, Elizabeth A Thiele, David J Kwiatkowski, Anat Stemmer-Rachamimov, Bence György, King-Hwa Ling, Masao Kaneki, Bakhos A Tannous, Vijaya Ramesh, Casey A Maguire, Xandra O Breakefield

Products/Services Used	Details	Operation
Plasmid DNA Preparation	… synthesis by GenScript Biotech (Piscataway, NJ, USA). AAV vector plasmid, AAV-CBA-cTuberin-c-Myc, was derived from the plasmid pAAV-CBA-W (56). This vector contains the CBA …	Get A Quote

摘要

Tuberous sclerosis complex (TSC) results from loss of a tumor suppressor gene - 1 or 2, encoding hamartin and tuberin, respectively. These proteins formed a complex to inhibit mTORC1-mediated cell growth and proliferation. Loss of either protein leads to overgrowth lesions in many vital organs. Gene therapy was evaluated in a mouse model of TSC2 using an adeno-associated virus (AAV) vector carrying the complementary for a "condensed" form of human tuberin (cTuberin). Functionality of cTuberin was verified in culture. A mouse model of was generated by AAV-Cre recombinase disruption of -floxed alleles at birth, leading to a shortened lifespan (mean 58 days) and brain pathology consistent with TSC. When these mic... More