Automated sequencing for culture-free diagnosis of drug resistant TB

Active Project Grant Awarded Last action

Award ID
R01AI176401
Recipient
Awarding agency
Obligated
$5,869,378

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 72% complete
Place of performance
La Jolla, CA 92037, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
While transformative, all-oral treatment regimens have recently been endorsed by world health organization (who) for the treatment of drug resistant TB (DR -TB), the efficacy of these new regimens is dependent on prior knowledge of the susceptibility profile of key drugs before treatment initiation. Companion molecular diagnostics for drug susceptibility testing (DST) of the new and repurposed anti-tuberculosis drugs is the most likely path to achieving practical and timely DST for these new regimens. However, there are currently no commercially available molecular diagnostics to detect mutations conferring resistance to bedaquiline, pretomanid, linezolid or delamanid, nor is there an easy developmental path forward using existing nucleic acid amplification test (NAAT) approaches given the complexity of the molecular targets for these drugs. Culture- free, next generation sequencing (NGS) has the greatest potential for delivering a comprehensive diagnostic solution, but existing workflows are highly complex, expensive, and rely on highly skilled staff to run them. To achieve broad adoption of NGS approaches, particularly in low resource settings, these workflows must be simplified substantially to reduce both their complexity and cost. Our goals for the proposed study are to bring culture-free NGS closer to patient care by simplifying NGS workflows for DR-TB diagnosis to the point that NGS can be run mostly hands-free by any laboratorian who can run a NAAT and to reduce costs by removing several enzymatic processes. Our objective is to demonstrate that automated, single amplification sequencing (ASAS) can be used to accurately diagnose resistance to all legacy and new/repurposed drugs for which there are recognized molecular targets (i.e., isoniazid, rifampicin, pyrazinamide, amikacin, moxifloxacin, bedaquiline, clofazimine, linezolid, and delamanid). We will achieve this objective by completing the following three aims; aim 1) expand with additional gene targets an existing single amplification targeted NGS assay and describe the assay performance; aim 2) integrate an existing akonni sputum extraction/PCR workstation with our novel single amplification sequencing assay and sequence on illumina ISEQ100; and aim 3) evaluate the accuracy of the ASAS solution for detection of drug resistance against a phenotypic and genotypic reference standard in sputum samples from patients at risk for DR-TB under field conditions at clinical laboratories in india, south africa, and moldova. The results of this project will demonstrate key characteristics of the ASAS workflow and will provide a solid developmental foundation for the application of this tool in clinical settings, reducing cost and time-to-result for comprehensive DST without culturing.

Transactions

Action Obligated Date
Amendment $664,261
Amendment $727,384
Amendment $727,384
Amendment $0
Amendment $728,822
Amendment $728,822
Amendment $0
Amendment $0
Amendment $764,235
Amendment $764,235
Original award $764,235
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Subawards

Subrecipient Amount Awarded
Akonni Biosystems Inc. Sub: 280,000.00 11/28/2023 Mod: 280,000.00 06/04/2024 Mod: 5,540.00 Mod: 154,000.00 09/05/2025 Statement of Work Akonni Biosystems Site PI: Christopher… $719,540
University Of Arkansas Mod: 48,007.00 3/4/2026 Mod: 52,626.00 02/19/2025 Sub: $67,590.00 10/12/2023 SCOPE OF WORK Subawardee: UNIVERSITY OF ARKANSAS Subaward Site PI: Donald Catanzaro… $168,223

Quick answers

Who received award R01AI176401?

R01AI176401 was awarded to University Of California, San Diego by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on April 17, 2023.

How much is award R01AI176401 worth?

$5,869,378 has been obligated on R01AI176401.

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