CHOP Develops STRIPE Technology for Rare Disease Diagnosis

Researchers at the Children's Hospital of Philadelphia (CHOP) have introduced a novel RNA sequencing strategy known as STRIPE, which utilizes targeted long-read RNA sequencing to enhance the diagnosis of rare diseases. This technology allows for the direct sequencing of full-length RNA molecules, providing insights into how genetic variants disrupt gene function. STRIPE aims to bridge the gap between genetic diagnosis and understanding disease mechanisms, thereby facilitating the development of targeted therapies.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis

The STRIPE platform has demonstrated its efficacy by successfully identifying disease-causing genetic variants in patients who had previously received inconclusive results from standard DNA testing. In a study published on April 15, 2026, in the journal *Science Advances*, STRIPE was applied to 88 individuals with congenital disorders of glycosylation (CDG) and primary mitochondrial diseases (PMD), as well as healthy controls. The technology not only re-identified known variants but also uncovered new disease-causing variants in five previously undiagnosed patients.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis

STRIPE builds upon CHOP's earlier TEQUILA-seq technology, designed to make RNA sequencing both cost-effective and scalable. The RNA-to-data cost for STRIPE is approximately $100 per sample, making it practical for clinical applications. Researchers have utilized STRIPE to analyze over 500 patients across various clinical programs at CHOP, showcasing its potential for widespread adoption in rare disease diagnostics.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis

Yi Xing, PhD, Associate Chief Scientific Officer for Omics, Technology & Engineering at CHOP, emphasized the importance of RNA in diagnosing rare diseases, stating, “RNA is a powerful modality for the diagnosis of rare diseases. By directly observing RNA molecules, we can obtain a more complete picture of how genetic variants alter gene products, in ways that DNA sequencing alone cannot reveal.” Lan Lin, PhD, who contributed to the development of TEQUILA-seq, noted that STRIPE enables ultra-deep sequencing at a scale suitable for clinical use.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis

Rebecca Ganetzky, MD, highlighted the challenges of obtaining disease-relevant tissues for RNA analysis, stating, “A major challenge in RNA-guided rare disease diagnostics is that disease-relevant tissues are often difficult to obtain from patients.” STRIPE addresses this by allowing high-quality analysis from accessible tissues like skin fibroblasts and blood.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis

Andrew C. Edmondson, MD, PhD, Founding Director of the CDG Clinic at CHOP, remarked on the collaborative benefits of STRIPE, indicating that it could validate new diagnoses for CDG patients while providing them access to innovative technology after standard testing failed. The researchers believe STRIPE represents a significant step toward RNA-based precision medicine, linking diagnostics to therapeutics for rare diseases.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis

The development of STRIPE technology at CHOP marks a significant advancement in the field of rare disease diagnostics. By providing a more comprehensive understanding of genetic variants through RNA sequencing, STRIPE has the potential to transform patient care and facilitate the development of targeted therapies in precision medicine.

CHOP Develops New RNA Sequencing for Rare Disease Diagnosis