RT Journal Article
SR Electronic
T1 Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabb1703
DO 10.1126/sciadv.abb1703
VO 7
IS 2
A1 Cheah, Pike-See
A1 Prabhakar, Shilpa
A1 Yellen, David
A1 Beauchamp, Roberta L.
A1 Zhang, Xuan
A1 Kasamatsu, Shingo
A1 Bronson, Roderick T.
A1 Thiele, Elizabeth A.
A1 Kwiatkowski, David J.
A1 Stemmer-Rachamimov, Anat
A1 György, Bence
A1 Ling, King-Hwa
A1 Kaneki, Masao
A1 Tannous, Bakhos A.
A1 Ramesh, Vijaya
A1 Maguire, Casey A.
A1 Breakefield, Xandra O.
YR 2021
UL http://advances.sciencemag.org/content/7/2/eabb1703.abstract
AB Tuberous sclerosis complex (TSC) results from loss of a tumor suppressor gene - TSC1 or TSC2, 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 TSC2 was generated by AAV-Cre recombinase disruption of Tsc2-floxed alleles at birth, leading to a shortened lifespan (mean 58 days) and brain pathology consistent with TSC. When these mice were injected intravenously on day 21 with AAV9-cTuberin, the mean survival was extended to 462 days with reduction in brain pathology. This demonstrates the potential of treating life-threatening TSC2 lesions with a single intravenous injection of AAV9-cTuberin.