LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding
Jonathan L. Schmid-Burgk,
Ricarda Maria Schmithausen,
Markus M. Nöthen,
Kerstin U Ludwig,
Posted 08 Apr 2020
bioRxiv DOI: 10.1101/2020.04.06.025635
Posted 08 Apr 2020
The ongoing SARS-CoV-2 pandemic has already caused devastating losses. Exponential spread can be slowed by social distancing and population-wide isolation measures, but those place a tremendous burden on society, and, once lifted, exponential spread can re-emerge. Regular population-scale testing, combined with contact tracing and case isolation, should help break the cycle of transmission, but current detection strategies are not capable of such large-scale processing. Here we present a protocol for LAMP-Seq, a barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) method that is highly scalable. Individual samples are stabilized, inactivated, and amplified in three isothermal heat steps, generating barcoded amplicons that can be pooled and analyzed en masse by sequencing. Using unique barcode combinations per sample from a compressed barcode space enables extensive pooling, potentially further reducing cost and simplifying logistics. We validated LAMP-Seq on 28 clinical samples, empirically optimized the protocol and barcode design, and performed initial safety evaluation. Relying on world-wide infrastructure for next-generation sequencing, and in the context of population-wide sample collection, LAMP-Seq could be scaled to analyze millions of samples per day. ### Competing Interest Statement J.S.-B., D.L., and F.Z. are inventors on a patent application filed by the Broad Institute related to this work with the specific aim of ensuring this technology can be made freely, widely, and rapidly available for research and deployment. F.Z. is a co-founder of Editas Medicine, Beam Therapeutics, Pairwise Plants, Arbor Biotechnologies, and Sherlock Biosciences. A.R. is a founder of Celsius Therapeutics, equity holder in Immunitas, and an SAB member for ThermoFisher Scientific, Syros Pharmaceuticals, Asimov, and Neogene Therapeutics. P.H. and M.M.N. are SAB members of HMG Systems Bioengineering GmbH. M.M.N. served on SABs for Lundbeck Foundation and Robert-Bosch-Stiftung, was reimbursed travel expenses by Shire GmbH, receives salary from and holds shares in Life & Brain GmbH.
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