Multimodal spatial transcriptomics integrates imaging, gene expression, CAG repeat length, huntingtin aggregates, DNA damage signals, and neuronal identity within the same cells and preserved tissue context, linking molecular events to neuron vulnerabilities in HD.

HD research is advancing through innovative techniques that study cells, models, human tissue, and big data to accelerate discovery and therapy development.

Long-read, PCR-free sequencing (PureTarget) enables exact measurement of CAG repeat length and its somatic expansions, including interruptions and copy-to-copy variability, which are not reliably captured by traditional PCR methods.

Cryo-electron tomography provides high-resolution 3D views inside frozen cells, revealing Huntington’s disease–related mitochondrial and protein aggregate changes not visible with conventional methods.

Single-molecule optical tweezers probe the energy landscape and conformations of huntingtin at the level of individual molecules, helping identify early structural changes linked to toxicity and assess effects of modifications or drugs.

Fluorescence-activated nuclei sorting (FANS) isolates the most vulnerable neuron types from brain tissue, enabling targeted analyses with diverse tools and shedding light on somatic CAG expansion in affected neurons.

Collectively, these technologies yield a more complete, cell-by-cell and molecule-by-molecule understanding of HD onset and progression, guiding biomarker discovery and therapeutic target identification.