C9orf72 RNA Foci Formation Assay Service

The GGGGCC repeat expansion in the C9orf72 gene is a critical factor in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Understanding the formation and dynamics of RNA foci resulting from this mutation is essential for advancing research and therapeutic development.

Our C9orf72 RNA Foci Formation Assay Service offers a cutting-edge, highly sensitive, and bidirectional detection solution. For further information regarding the products and services provided, project-specific consultation, and pricing, please submit an inquiry here.

C9orf72 RNA Foci Formation in ALS

The hexanucleotide GGGGCC repeat expansion in the C9orf72 gene is a major genetic determinant of ALS and FTD, contributing to approximately 50% of familial cases. This repeat expansion leads to the production of both sense and antisense transcripts, which subsequently form nuclear RNA foci. These RNA foci are implicated in a complex array of pathological mechanisms, including RNA toxicity. The sequestration of RNA-binding proteins by these foci disrupts normal RNA processing, potentially leading to aberrant protein expression and cellular dysfunction. Furthermore, the regional and cellular heterogeneity of RNA foci distribution suggests a complex relationship between foci formation and neuronal vulnerability.

C9orf72 RNA Foci Formation Assays

• Quantification and Localization of RNA Foci

Our service can accurately detect the number, distribution, and dynamic changes of sense/antisense RNA foci in the nucleus (e.g., frontal cortex, cerebellar granule cells, and other regions), providing data to analyze the association between RNA foci and pathological characteristics (e.g., neuron specificity and disease progression).

Fig.1 In c9FTD/ALS, transcripts containing the C9ORF72 hexanucleotide repeat expansion accumulate as nuclear RNA foci, notably within the frontal cortex, spinal cord, and cerebellum.^{2, 3}

• Validation of Therapeutic Targets

Several studies have confirmed that antisense oligonucleotides (ASOs) targeting degradation of RNA foci can reduce toxicity, but they must simultaneously target bidirectional transcripts. Our detection service can evaluate the clearance effect of ASOs or other small molecule drugs on sense/antisense foci and accelerate the optimization of treatment strategies.

• Combined Analysis

A combined analysis of RNA foci and RAN proteins (such as poly-PR and poly-GP) through co-localization studies offers a more comprehensive assessment of the pathological burden associated with C9orf72 mutations.

• Cell Model Validation

Our services facilitate the detection of RNA foci in both neuronal and non-neuronal cell types, including fibroblasts and induced pluripotent stem cell-derived motor neurons. This enables the simulation of RNA foci distribution within critical patient brain regions, such as the frontal cortex and spinal cord. Notably, RNA foci are consistently observed in motor neurons differentiated from patient-derived iPSCs, and we provide support for phenotypic validation of these models.

The C9orf72 RNA Foci Formation Assay Service is a valuable tool for studying neurodegenerative diseases such as ALS/FTD. Our technology platform boasts high sensitivity, multi-dimensional analysis capabilities, and a wide range of sample applicability, providing customers with comprehensive and accurate research support. If you are interested in learning more about our services, please do not hesitate to contact us.

References

1. Kumar, Vijay, Gulam M. Hasan, and Md Imtaiyaz Hassan. "Unraveling the role of RNA mediated toxicity of C9orf72 repeats in C9-FTD/ALS." Frontiers in neuroscience 11 (2017): 711.
2. Gendron, Tania F., et al. "Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS." Acta neuropathologica 126 (2013): 829-844.
3. Distributed under Open Access license CC BY 4.0, without modification.