The DIGET Program Overview
The Department of Defense (DoD) requires timely and comprehensive threat detection to support overall readiness, counter the spread of disease, and promote stabilization missions. The “Detect It with Gene Editing Technologies” (DIGET) program aims to deliver this capability, leveraging advances in gene editing technologies to develop low-cost, high-trust, rapidly reconfigurable, and fieldable diagnostic (Dx) and biosurveillance (BSV) technologies to enable detection of any threat, anytime, anywhere.
To achieve its goal, DIGET will design, develop, prototype, and deploy two novel nucleic acid detection devices for the simultaneous detection of multiple targets: 1) a disposable point-of-need diagnostic for up to 10 targets, and 2) a massively multiplexed detection (MMD) device for 1,000 or more targets. Both devices must be simple to operate, low-cost, and rapidly reconfigurable to provide high impact, high quality, trusted information that enhances decision-making. The disposable point-of-need device will improve the speed and efficacy of triage and treatment and enhance the standard of care for the military and public health domains, and the MMD device will enable early threat detection, assess disease severity, and improve situational awareness. The MMD platform will also provide actionable data for biosurveillance efforts such as characterization of known and emergent pathogens in circulation to inform countermeasure deployment.
The DIGET program will focus on two primary technical thrusts. The first focuses on the foundational chemistries and technology required to build a flexible detection assay that meets or exceeds current gold-standard assay sensitivity and specificity performance, while maintaining a simple and deployable workflow. This will require the design, development, and optimization of gene editing enzymes and reporters to detect targets and amplify assay signal to support sample to answer times of ≤ 15 minutes. Further, a robust and adaptable bioinformatics pipeline is needed to design programmable probes/guides for both broad target sequences (i.e., sequences that are present across a number of strains/biomarkers) and specific target sequences (i.e., unique sequences that can identify subtype, rare mutations, and host biomarkers of disease severity).
The chemistries developed under the first technical thrust will provide a detection and measurement foundation to support the second technical thrust, which focuses on development of novel hardware technologies to package the assays into field-forward, deployable, and interoperable devices that address both the point-of-need and MMD platforms. The point-of-need device will require materials and surface chemistry optimization to produce a visual, unambiguous output for ≥10 targets. The MMD device will incorporate a disposable cartridge for integrated sample preparation and assay reagents/fluidic components necessary for single-step operation by the user. A companion device will read the results from the cartridge and house a back-end computational workflow that will transform the results for each of the ≥1000 target tests into a simple report on pathogen characterization and/or host response. Data from the MMD device will also be concurrently uploaded to a BSV repository for further analysis and trend prediction. The resulting DIGET technologies must be versatile enough for use in active combat zones, disaster response, and Role/Echelon 1 (point-of-need) and Role/Echelon 2 (MMD) medical settings worldwide.
