# TB Phage therapy: Optimizing delivery methods of mycobacteriophages to target intracellular Mycobacterium tuberculosis

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $210,000

## Abstract

Abstract
Tuberculosis (TB) remains as a major global health problem causing 1.2 million deaths and over 10
million new cases each year. The onset of the HIV epidemic beginning in the late 1980s led to immune
suppression in humans and significantly increased the emergence of drug resistance, lengthening
treatment duration. Ominously, there are strains of M. tuberculosis, the causative agent of TB, that are
resistant to many, if not all, of the currently available TB drugs that are extremely difficult to treat. As an
alternative to drugs, mycobacteriophages - viruses that kill M. tuberculosis, have been considered as
possible agents to treat tuberculosis. However, previous studies have had limited success in mammalian
hosts. The goal of this grant is to elucidate why phage therapy fails to work. We hypothesized that the
major obstacle is mycobacteriophages are unable to come into contact with the M. tuberculosis cells
that live intracellularly. We propose to develop novel strategies to deliver mycobacteriophages to the
intracellular compartments in which M. tuberculosis resides. One approach would be to engineer
mycobacteriophage capsid proteins so that we can add macrophage delivery ligands to promote cellular
uptake. In addition, we plan to explore the use of a Mycobacterium smegmatis strain as a Trojan horse
delivery vector to the intracellular M. tuberculosis. These studies will be enhanced by our ability to
generate mycobacteriophages that express fluorescent reporter proteins. In order to deliver the
mycobacteriophages to the lungs, the site of intracellular localization, we plan to use spray dried
mycobacteriophage powders. We also plan to test the hypothesis that mycobacteriophages may work as
an adjunct therapy with existing TB drugs in mouse models.

## Key facts

- **NIH application ID:** 10312824
- **Project number:** 5R21AI156853-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** WILLIAM Robert JACOBS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $210,000
- **Award type:** 5
- **Project period:** 2020-12-07 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312824

## Citation

> US National Institutes of Health, RePORTER application 10312824, TB Phage therapy: Optimizing delivery methods of mycobacteriophages to target intracellular Mycobacterium tuberculosis (5R21AI156853-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10312824. Licensed CC0.

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