Rapid detection of TB from blood using cell-free DNA and crispr
Active Project Grant Awarded Last action
- Award ID
- R01AI174964
- Recipient
-
University Of California, San Diego UEI UYTTZT6G9DT1
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,949,803
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 82% complete
- Place of performance
- La Jolla, CA 92037, USA
Award details come from USAspending.gov.
Description
- Abstract
- While >90% of TB cases are curable, treatment is dependent on diagnostics based exclusively on the detection of mycobacterium tuberculosis (MTB) in patient sputum, despite the limitations of sputum as a diagnostic sample. Sputum is difficult to process, almost impossible to obtain from patients with paucibacillary TB, such as people living with HIV (plwh) and children and is not diagnostic for patients with extrapulmonary TB. A low- cost, rapid test using blood instead of sputum could transform TB diagnosis for all patients and reduce the current diagnostic GAP between patients with and without HIV CO-infection. Most active TB disease (ATB) is still diagnosed with sputum smear microscopy, despite its low sensitivity and specificity. This lack of diagnostic rigor contributes to the ongoing underdiagnosis of ~3 million TB cases/year, resulting in continued transmission and poor patient outcomes, especially among plwh in whom mortality is highest. Our long-term goal is to transform TB diagnosis with a blood test that accurately distinguishes patients with ATB from latent TB infection (ltbi), and other pulmonary disorders regardless of CO-infection with HIV. The objective of this study is to demonstrate the analytical and clinical performance of a novel assay for rapid diagnosis and treatment monitoring of ATB that exploits the precise molecular affinity of crispr and promiscuous nuclease activity of CAS12A to detect ultra-low concentrations of MTB cell free DNA (cfdna) circulating in blood. Preliminary analytical studies indicate assay detection limits of 90%), and high diagnostic sensitivity (85%) in children. We will achieve our proposed objective through the following specific aims: aim 1: validate a lateral flow version of the crispr-TB assay for low resource settings. Our current working assay requires a PCR step and fluorescence reader. Preliminary studies indicate we can significantly simplify this workflow using isothermal amplification and a novel lateral flow (LF) strip for detection of MTB cfdna. We will expand on our pilot studies to validate the existing LF assay using contrived and clinical samples. Aim 2: define the dynamics of the MTB cfdna signal for treatment monitoring. Preliminary studies indicate the MTB cfdna signal decreases to extinction after treatment initiation but can have non-linear dynamics. We will define the variability and trajectory of the MTB cfdna signal in biobanked serial samples from 34 patients treated for drug resistant TB over a year, and 50 prospectively collected patients with drug susceptible TB treated over six months. Aim 3: determine the clinical sensitivity and specificity of the crispr-TB assay in field settings. We will prospectively collect and test blood samples from 450 patients at risk for TB in TB-endemic field settings with high (south africa), medium (pakistan) and low (mexico) HIV burden.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $695,846 | |
| Amendment | $718,939 | |
| Amendment | $739,826 | |
| Original award | $795,192 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of Arkansas | $228,203 | |
| National TB Control Program | $41,043 | |
| The Administrators Of Tulane Educational Fund | $770,827 |
Quick answers
Who received award R01AI174964?
R01AI174964 was awarded to University Of California, San Diego by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 17, 2023.
How much is award R01AI174964 worth?
$2,949,803 has been obligated on R01AI174964.
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