AAV-mediated adenine base editing construct for CLN2

AAV-mediated adenine base editing construct for CLN2 is an experimental gene therapy candidate being developed by researchers at Weill Cornell Medicine for the treatment of late infantile ceroid lipofuscinosis (CLN2 disease). The therapy utilizes an adenine base editor (ABE) delivered via a dual split-intein AAV vector system, typically employing the neuron-tropic AAVrh.10 capsid. It is specifically designed to correct the c.622C>T (p.R208X) nonsense mutation in the CLN2 gene, which causes a deficiency in the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). By performing a precise A-to-G conversion on the non-coding strand (effectively T-to-C on the coding strand), the editor restores the production of functional TPP1 enzyme. Preclinical studies in R207X mouse models have demonstrated successful rescue of CLN2 mRNA levels and restoration of TPP1 enzymatic activity, providing proof of concept for this approach in treating neurodegenerative lysosomal storage disorders.

Other names

AAVrh.10-ABE-CLN2adenine base editing construct for CLN2