Scientific Ecosystem
Where We Are Now: Advancing Toward Targeted Therapy
The Sweet Geej initiative is currently focused on the design, development, and safety of an upregulation antisense oligonucleotide (ASO) therapy.
Our goal is to increase expression from her healthy copy of the NAA15 gene, supporting neurological development and functional regulation.
Current Progress: Advancing Lead ASO Candidates
We are actively advancing a set of precision ASO candidates through targeted screening and validation in collaboration with specialized partners, with primary discovery work led by La Jolla Labs (LJL).
ASO Discovery and Translational Optimization (La Jolla Labs)
Our work at LJL is focused on identifying ASO sequences that increase expression of the NAA15 gene and translate that signal into meaningful protein production.
80 ASO candidates were designed and screened across key regulatory regions of the gene
Multiple candidates demonstrated robust mRNA upregulation, with top performers exceeding 150–200% increase over baseline
Dose-response studies confirmed consistent, reproducible activity across leading candidates
Protein-level validation has now been achieved across multiple candidates, demonstrating that increases in mRNA expression can translate into increased NAA15 protein levels
This combined RNA and protein signal represents a critical milestone in identifying viable therapeutic candidates and narrowing toward a lead sequence.
Translational Validation in Patient-Derived Cells (iXcells)
In parallel, we are advancing evaluation of top ASO candidates in GG’s patient-derived iPSC neurons through iXcells.
This work is designed to confirm performance in a disease-relevant human system and includes:
Testing in both glutamatergic and GABAergic neurons
Measurement of gene and protein expression in a patient-specific context
Functional assessment of neuronal behavior and network activity with lead ASO sequence candidates
This stage provides an essential bridge between early discovery and in vivo development.
This work is designed to move thoughtfully from molecular insight to therapeutic readiness. While centered on GG, the knowledge gained may also inform broader understanding of NAA15-related conditions and haploinsufficiency-driven neurodevelopmental disorders.