Project Application

Tackling Real-World Problems

Core Technology and Platform

NeuroSplice is a toehold switch–based diagnostic designed to detect the IL7R exon-6–skipping splice isoform associated with Multiple Sclerosis (MS).

By combining programmable RNA sensors with cell-free TXTL, NeuroSplice delivers a rapid, portable molecular readout that seamlessly integrates with existing diagnostic workflows.

Conceptual diagram of a toehold switch RNA sensor activating gene expression.

Our platform relies on a sophisticated dry-lab pipeline for design, including RNA folding prediction (NUPACK, RNAstructure), thermodynamic validation, and off-target screening (BLAST). This approach allows the system to be rapidly extended to other splicing events implicated in autoimmune and neurological disorders.

Envisioned Application Areas

1 Point-of-Care Triage for Neuro-inflammatory Workups

Image of a rapid paper-based diagnostic device.

What it is: A rapid RNA screen detecting IL7R delta-6 isoforms in peripheral samples as an adjunct to MRI and CSF analysis. Lumbar puncture and imaging remain diagnostic standards, but a molecular front-end could help prioritize who should receive expedited workups (Thompson et al., 2018).

Why it matters: Triage speed is especially critical in regions with limited MRI availability or delayed specialist access. A lightweight RNA-based test could help shorten time-to-diagnosis.

2 Disease Activity Tracking & Risk Stratification

What it is: Periodic monitoring of IL7R exon-6 splicing patterns as a molecular adjunct to clinical relapse data and imaging intervals.

Molecular diagram showing the difference between full-length and soluble IL7R production via splicing.

Why it matters: Exon-6 exclusion produces soluble IL7R (sIL7R), which potentiates IL-7 signaling and amplifies autoreactive T-cell responses—mechanisms linked to MS progression (Gregory et al., 2007; Galarza-Maldonado et al., 2020). A simple molecular assay could provide a window into disease activity between scans.

3 Companion Diagnostic for Splicing-Modulating Therapies

What it is: A companion assay for antisense oligonucleotides (ASOs) designed to modulate IL7R splicing. NeuroSplice can verify splicing shifts, guide dose-finding, and stratify patients by baseline splicing state (Harvey et al., 2022).

Why it matters: Preclinical studies show ASOs can bidirectionally tune IL7R exon-6 splicing in human T cells. A low-cost RNA sensor that mirrors these splicing outcomes could accelerate translation into clinical trials.

4 High-Throughput Research Screens for Splice Biomarkers

Image of a 96-well plate combined with an overlay of RNA folding simulation data.

What it is: A scalable platform to rapidly design and test panels of toeholds targeting splice variants across autoimmune and neurological diseases. Our computational workflow—combining delta G thresholds, RBS exposure analysis, and off-target filtering—enables efficient multiplexing (Zadeh et al., 2011).

Why it matters: Expanding from a single isoform to multi-marker signatures could improve specificity and predictive power, while maintaining the portability of paper-based TXTL assays (Pardee et al., 2016).

5 Curriculum-Ready Outreach & Health Literacy

What it is: Integration into STEM education kits and age-adapted children’s books to explain RNA diagnostics, splicing, and autoimmune disease. Pilots with teachers, nurses, and biology instructors confirm the feasibility of presenting NeuroSplice in preschool through high-school classrooms.

Why it matters: Increasing public literacy about immune health and diagnostics reduces stigma, fosters trust in new technologies, and inspires the next generation of biomedical innovators.

Future Visions

Multi-Target Panels

Deploy parallel toeholds for IL7R Δ6 and co-regulated cytokine RNAs to boost diagnostic accuracy and reduce false positives.

Clinical Pathway Integration

Expand from labs to emergency departments, mobile clinics, and tele-neurology pathways.

Therapeutic Pairing

Real-time monitoring of exon-6 splicing during ASO to accelerate optimization and precision targeting.

References

Doudna, J.A., & Charpentier, E. (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096.
Galarza-Maldonado, C., et al. (2020). IL7R exon-6 polymorphisms and multiple sclerosis susceptibility. Journal of Neuroimmunology, 346, 577310.
Gregory, S.G., et al. (2007). Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nature Genetics, 39(9), 1083–1091.
Harvey, R.J., et al. (2022). Antisense oligonucleotides for therapeutic modulation of IL7R splicing. Molecular Therapy – Nucleic Acids, 27, 189–201.
Pardee, K., et al. (2016). Paper-based synthetic gene networks. Cell, 165(5), 1255–1266.
Thompson, A.J., et al. (2018). Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurology, 17(2), 162–173.
Zadeh, J.N., et al. (2011). NUPACK: Analysis and design of nucleic acid systems. Journal of Computational Chemistry, 32(1), 170–173.