smMIP Lysosomal storage disorder gene panel
Bridging affordability with cutting edge diagnostics for rare diseases
Outcomes
83%
Highest diagnostic yield of any genetic assays for lysosomal storage disorders
2
SNVs and CNVs detected in a single test
3
Days from library preparation to results
1
National patent
Overview
Lysosomal storage disorders are a collection of 70 rare genetic disorders that affect 1 in 5000 children worldwide. They are diagnosed based on clinical symptoms and a complex set of biochemical tests, which make their diagnosis laborious, expensive and prolonged. Together with FRIGE Institute of Human Genetics, we developed India’s first targeted sequencing panel for these diseases.
Working together, we created a sequencing panel inspired by the single molecule molecular inversion probe (smMIP) technology that is able to detect single nucleotide as well as copy number mutations simultaneously with high accuracy. Our approach makes diagnosis of these diseases affordable, accurate and high throughput.
3 Big Takeaways
Improvement in diagnosis
Genetic makeup of lysosomal storage disorders is marred with complex mix of single nucleotide variants, copy number variants and complex structural variants. A set of biochemical and genetic tests are currently used in the clinic to diagnose these diseases. However, they require skilled manpower, complex laboratory setup and a priori knowledge for manual interpretation. To improve diagnostic yield, we distilled these challenges into core elements and created a unique blend of molecular inversion probes with computational systems to analyse DNA with high accuracy.
Each probe is carefully designed to capture contents of the DNA with high precision. Our team inserted a degenerate molecular barcode to tag each capture event. This helps reduce sequencing errors by several fold and analyse copy numbers of the DNA targets.
The result is an assay with high-throughput screening of DNA targets for a plethora of mutation types.
Figure showing diagnostic yield of the assay by disease type (Sheth et al 2024).
Development of easy to use assay
Previous biochemical and genetic tests relied on rigid and iterative systems with limited opportunity to screen all lysosomal storage disorders simultaneously. Our laboratory and computational teams collaborated with FRIGE Institute of Human Genetics to build a new, flexible architecture of targeting DNA molecules based on molecular inversion probes.
To help make the entire assay feel seamless, we created a suite of modular components for sequencing library preparation, sequencing and post-sequencing computational analysis. Having a consistent, flexible system helped reduce laboratory capex, over-reliance on manual interpretation and hands-on time in the lab.
This in turn helped create a high-throughput and cost effective assay with a diagnostic yield of 83% and turnaround time of 3 days from library preparation to reporting.
Figure showing the ability of the assay to detect CNVs (Sheth et al 2024).
Unique application in newborn screening
With high target capture efficiency and accuracy, the assay is able to screening DNA with as little input as 20ng. Clinical labs in the domain of newborn screening can utilise the assay on DNA extracted on dried blood spot cards for lysosomal storage disorder diagnosis.
This would allow doctors to initiate treatment regiment for children with this diseases even before the symptoms emerge.
After launch
FRIGE-Sanofi DISHA program
Our assay powers the landmark FRIGE-Sanofi Disha program that offers free-of-cost diagnosis for 5 common lysosomal storage disorders across India.You can avail the program by contact here.
Assay commercialization
Our assay is undergoing commercialization with Trivitron Healthcare Pvt. Ltd. in order to bring the power of the assay to the entire genomics marker across India. Together, we are undergoing CDSCO IVD certification for the highest quality in vitro diagnostics certificate for genetic tests in India.