Dolan Sondhi

TL;DR: This work illustrates that expressed protein ligation is a simple and powerful new method in protein engineering to introduce sequences of unnatural amino acids, posttranslational modifications, and biophysical probes into proteins of any size.

TL;DR: Assessment of the primary outcome variable suggests a slowing of progression of LINCL in the treated children, and it is proposed that additional studies to assess the safety and efficacy of AAV-mediated gene therapy for LINCL are warranted.

TL;DR: AAVrh.10CLN2-treated CLN2(-/-) mice had significant reduction in CNS storage granules and demonstrated improvement in gait, nest-making abilities, seizures, balance beam function, and grip strength, as well as having a survival advantage.

TL;DR: It is demonstrated that AAV-mediated TPP1 enzyme replacement corrects the hallmark cellular pathologies of cLINCL in the mouse model and raises the possibility of using AAV gene therapy to treat c LINCL patients.

TL;DR: The strategy of this clinical study is based on the concept that persistent expression in the CNS of the normal CLN2 cDNA with production of sufficient amounts of TPP-I should prevent further loss of neurons, and hence limit disease progression, and that administration of the AAV2cuhCLN2 vector will slow down or halt the progression of the disease in the central nervous system.