Ensilication preserves high-molecular weight native DNA for clinical long-read sequencing

Encapsulation of native DNA in silica matrices preserving molecular integrity and epigenetic modifications without cold-chain infrastructure

Ensilication — encapsulation of DNA in silica matrices — preserves native high-molecular-weight DNA at ambient temperature for 30 days with sequencing performance equivalent to -80°C freezing. Across three Genome-in-a-Bottle reference genomes, ensilicated and frozen samples showed no significant differences in read length (N50 ~8,000-11,000 bp), variant-calling accuracy, or CpG methylation. Clinically, this method resolved diagnosis in two patients with rare genetic diseases, including a variant in the segmentally duplicated GTF2I locus and a methylation pattern consistent with KDM2A-related disorder. Ensilication eliminates cold-chain dependency for diagnostic long-read sequencing.

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Cold-chain dependency is one of the main obstacles to deploying long-read sequencing in rare disease diagnostics, particularly in middle-income countries. Ensilication could transform sample collection and transport logistics. The two clinical diagnoses resolved in this study — including a segmentally duplicated locus — concretely illustrate the added value of this approach.