# Handheld and population-based sequencing for rapid detection of new and repurposed drug resistance in M. tuberculosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $793,285

## Abstract

PROJECT SUMMARY / ABSTRACT
Rifampin-resistant tuberculosis (RR-TB) remains a global public health crisis. Molecular TB assays such as Xpert
have led to dramatic increases in RR-TB case detection and ongoing expansion of the global estimated need for
newer treatments. Tremendous financial and scientific resources are directed toward the investigation of new
and repurposed drugs, but efforts to optimize and scale-up shorter course, all-oral RR-TB regimens are hindered
significantly by the scarcity of availability and access to phenotypic or molecular susceptibility testing for these
agents. Longstanding critical barriers of routine phenotypic drug susceptibility testing include prolonged
turnaround time and infrastructure requirements that preclude efficient scale-up, contributing significantly to the
DR-TB diagnostic gap. Patients are often committed to months of ineffective treatments, leading to acquisition
of further drug resistance through selective drug pressure and worse clinical outcomes. Our goal in proposing
this work is to improve patient outcomes through strategic and evidence-based use of genomics tools in high
burden settings. We will leverage collaborations with international non-profit organizations, a South African MRC-
funded cohort, and commercial partners to translate our established targeted deep sequencing assay onto a
cost-efficient, handheld nanopore-based sequencing platform (Aim 1, near-clinic solution); and prospectively
sequence patient samples early in the course of their treatment in two diverse geographic regions with differing
RR-TB and HIV epidemics (Aim 2, centralized solution). These efforts will translate modern-day pathogen
genomics into population benefits and contribute to extending the effective lifespan of hard fought new and
repurposed anti-TB drugs.

## Key facts

- **NIH application ID:** 10177697
- **Project number:** 1R01AI153213-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David M Engelthaler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $793,285
- **Award type:** 1
- **Project period:** 2021-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177697

## Citation

> US National Institutes of Health, RePORTER application 10177697, Handheld and population-based sequencing for rapid detection of new and repurposed drug resistance in M. tuberculosis (1R01AI153213-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10177697. Licensed CC0.

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