Research
Gene Replacement Therapy Feasibility
Dr. Erin Eun-Young Ahn, Ph.D.
University of Alabama at Birmingham
Started January 2025
Funding
Feasibility and preclinical proof-of-concept phase
Assessing the feasibility of delivering a functional copy of the SON gene to affected cells using viral vector technology, with preclinical proof-of-concept studies planned in mouse models.
Gene replacement therapy aims to deliver a working copy of the SON gene directly to affected cells, addressing the root cause of ZTTK syndrome rather than its downstream symptoms. Because ZTTK results from haploinsufficiency — having only one functional gene copy — supplementing cells with an additional functional copy could theoretically restore normal SON protein levels.
The primary technical challenge is the large size of the SON coding sequence (over 7,000 base pairs), which exceeds the packaging capacity of standard adeno-associated virus (AAV) vectors commonly used in gene therapy. This project evaluates alternative delivery strategies including dual-vector approaches and emerging large-cargo vector platforms.
Alongside gene replacement, the team is assessing antisense oligonucleotide (ASO) approaches that could stabilize existing SON mRNA and gene-modulating small molecules that could upregulate expression from the remaining functional SON copy. These parallel therapeutic strategies increase the probability that at least one viable treatment path emerges.