GENE REPLACEMENT THERAPY PROGRAM
Urbagen is being developed to be a single-dose, preservative-free, sterile, intrathecal infusion of non-replicating, single-stranded AAV9 vector.
It contains the human CTNNB1 gene, which encodes for the beta-catenin protein, under the control of the cytomegalovirus-enhanced chicken-beta-actin hybrid (CBh)/Neuron-specific synapsin1 (SYN1) promoter.
The size of the packaged single-stranded vector genome is ~4.7 kb.
Within our project, more than a dozen therapeutic CTNNB1 gene therapy variants with the CBh/SYN1 promoter have been designed, and some of them have passed early in silico evaluation and are being cloned for in vitro and in vivo evaluation.
These are the constructs that we are testing in iNPCs in order to triage the best ones for in vivo assessment. Within each candidate we are systematically evaluating regulatory elements in both the coding and non-coding components to ensure both therapeutic efficacy and safety profiles of any therapeutic lead.