# CRISPR-TB for pediatric TB diagnosis and treatment response

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $742,227

## Abstract

PROJECT SUMMARY/ABSTRACT
Children under 5 years of age account for ~50% of the 1.2 million new cases of pediatric TB each year, but are
least likely to be diagnosed, and are at highest risk of death without prompt treatment. Young children are more
likely to present with disseminated or extrapulmonary TB and paucibacillary disease, often missed by respiratory
sampling and our currently available diagnostics. Non-sputum diagnostic tools for TB detection and treatment
response in young children, using easily obtained specimens are urgently needed.
Our team has successfully developed an ultra-sensitive CRISPR-based approach (CRISPR-TB) that detects M.
tuberculosis (Mtb) cell free DNA (cfDNA). In pilot evaluation with repository blood samples, CRISPR-TB
demonstrated high sensitivity (94%) and specificity (95%) among adults and children with TB and their
asymptomatic household contacts in Eswatini. Among hospitalized Kenyan children with HIV (median age 2
years), CRISPR-TB detected 100% with microbiologically confirmed TB, and an additional 85% with clinically
diagnosed TB (i.e. missed by respiratory-based diagnostics).
We now propose to expand CRISPR-TB evaluation in a large prospective cohort of 400 children with suspected
TB (majority <5 years) to evaluate CRISPR-TB diagnostic performance (Aim 1) including longitudinal evaluation
for treatment response (Aim 2), and extend evaluation to urine samples (Aim 3). Additional cohorts of adults with
confirmed TB and their asymptomatic household controls, and recently BCG-immunized asymptomatic infants
will be evaluated. Exploratory aims will pilot a POC platform, assess utility of CRISPR-TB to identify early
incipient or subclinical disease in participants with missed diagnosis at baseline who develop incident TB, and
estimate “true” prevalence of pediatric TB using Bayesian latent class analysis given imperfect reference tests.
We hypothesize CRISPR-TB will have similar/improved diagnostic performance to Xpert on respiratory samples
among children with confirmed TB without the need for sputum, and identify additional children missed by
respiratory samples, will provide a useful surrogate marker of treatment response with decline in quantitative
levels during successful treatment, and be adaptable to urine samples.

## Key facts

- **NIH application ID:** 10774550
- **Project number:** 1R01AI179714-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sylvia LaCourse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $742,227
- **Award type:** 1
- **Project period:** 2024-07-11 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10774550

## Citation

> US National Institutes of Health, RePORTER application 10774550, CRISPR-TB for pediatric TB diagnosis and treatment response (1R01AI179714-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10774550. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*