activating antisense oligonucleotide targeting ADNP

An activating antisense oligonucleotide (ASO) designed to treat ADNP syndrome (also known as Helsmoortel-Van Der Aa syndrome) by increasing the translation efficiency of the ADNP gene. Developed by researchers at the University of California, Davis, this therapeutic candidate targets inhibitory elements within the 5' untranslated region (5'UTR) of ADNP mRNA, such as secondary structures and upstream open reading frames (uORFs), which normally suppress translation of the primary open reading frame. By blocking these elements, the ASO restores levels of the activity-dependent neuroprotective protein (ADNP), a multifunctional regulatory protein and transcription factor essential for brain development and epigenetic regulation. Preclinical data presented at ASGCT 2026 demonstrated that several ASO candidates could increase ADNP protein levels by 2-4-fold in human iPSC-derived neural progenitor cells and differentiated neurons, a range intended to rescue the haploinsufficiency characteristic of the disorder.

Other names

activating ASO targeting ADNP