Using RNAscope™ ISH Technology to Advance ALS Gene Therapy

Advancing ALS Gene Therapy Through Quantitative RNA Analysis

Dr. Alessandro Moro is developing novel gene therapies for amyotrophic lateral sclerosis (ALS), focusing on TDP-43 protein pathology in motor neurons. His team at VectorY Therapeutics uses patient-derived motor neurons to model disease, aiming to determine optimal therapeutic transgene expression levels.  

Dr. Moro needed to analyze intrabodies (intracellular antibodies), which cannot be detected with conventional antibody methods. Without a solution for quantifying transgene expression across multiple model systems, from cell culture to animal models, translating promising lab results to clinical success remained uncertain.

Solving Gene Therapy's Translation Challenge with RNAscope 

RNAscope in situ hybridization technology provided the quantitative precision Dr. Moro's team needed. 

"We're using RNAscope as a bridge between in vitro and in vivo research," explains Dr. Moro. "What really made RNAscope stand out was the signal-to-noise ratio," notes Dr. Moro. "The images are really easy to analyze, easy to quantify." 

RNAscope has enabled the VectorY team to: 

• Quantify therapeutic transgene expression at single-cell resolution to establish threshold levels needed for phenotypic rescue in patient-derived motor neurons. 
• Maintain consistency across model systems, from cell culture to mouse models to non-human primates, using the same probes and protocols. 
• Optimize gene therapy biodistribution by revealing exactly which cells are transduced and at what expression levels after vector injection. 
• Multiplex cell-type markers to simultaneously assess transgene expression, cell identity, and immune infiltration in single panels.

Data-Driven Dose Optimization for Safer, More Effective Therapies 

This quantitative approach directly informs critical development decisions, minimizing risks of under-dosing (treatment failure) or over-dosing (adverse effects). The technology's clear imaging has also facilitated communication with regulatory experts and clinical development teams. 

Looking ahead, Dr. Moro is exploring RNAscope for antisense oligonucleotide (ASO) detection and target engagement studies. His recommendation to other researchers? 

"Spend the time to get familiar with the protocols and everything you can do with it. It's really an entire universe of possibilities. Talk with the field scientists, really get the most out of the technology. Definitely give it a try, there's no reason why not to."

About RNAscope ISH Technology  

RNAscope in situ hybridization technology enables single-molecule RNA visualization in intact cells and tissues with exceptional sensitivity and specificity. RNAscope provides single-cell resolution gene expression analysis across diverse sample types, accelerating discovery in neuroscience, oncology, gene therapy development, and beyond.

Discover RNAscope 

Learn how RNAscope ISH can advance your gene therapy research.