Phaige therapy center: AI-guided tailspike engineering and molecular typing for rapid phage design and testing against eskape pathogens

The National Institute of Allergy and Infectious Diseases awarded the J. David Gladstone Institutes $2,047,959 on May 11, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to establish the Phaige Therapy Center, developing AI-guided molecular tools and preclinical assays for rapid bacteriophage design and testing against multidrug-resistant ESKAPE pathogens with a focus on Klebsiella pneumoniae.

The award funds two primary research projects. Project 1 develops high-throughput, sequencing-based assays to measure quantitative rate constants across each phase of the phage infection cycle—recognition, entry, replication, packaging, and lysis—enabling rational selection and engineering of phages with superior efficacy. Project 2 employs multiplexed assays to rapidly characterize K. pneumoniae strains by capsule type and susceptibility profile, supporting the creation of optimized, off-the-shelf phage cocktails tailored to individual clinical isolates.

The center operates two specialized cores alongside an administrative core. The Advanced Computational Core combines bioinformatics pipelines, AI-driven modeling, and machine learning to predict phage-host interactions and guide phage selection. The Organoid and Human Cell Culture Core incorporates 3D human tissue models and primary cell cultures into early screening to capture host-pathogen dynamics overlooked by standard in vitro assays. The Administrative Core manages development and research program activities supporting pilot projects and coordinates with clinical and industry advisors.

Work is performed in San Francisco, California, with a period of performance from May 11, 2026, through April 30, 2031.

Abstract

The gladstone phaige therapy center seeks to address the critical threat of multidrug-resistant eskape pathogens by developing next-generation preclinical assays and computational tools. Our overarching goal is to establish a robust, quantitative, and predictive preclinical framework that accelerates the pipeline from phage discovery to clinical application, with a primary focus on klebsiella pneumoniae. Specifically, project 1 develops high-throughput, sequencing-based assays to measure rate constants for each component of the phage infection cycle (recognition, entry, replication, packaging, and lysis). By capturing granular, quantitative data, this work will enable the rational selection and engineering of phages that exhibit superior efficacy. Project 2 employs multiplexed assays to characterize k. Pneumoniae strains rapidly by their capsule types and susceptibility profiles. Integrating capsule-typing with systematic phage compatibility testing will allow for the creation of optimized, off-the-shelf phage cocktails tailored to individual clinical isolates. The center's strategy includes two specialized cores to ensure translational relevance and efficiency. The advanced computational core combines bioinformatics pipelines, AI-driven modeling, and machine learning to predict phage-host interactions and guide phage selection. The organoid and human cell culture core incorporates 3D human tissue models and primary cell cultures into early screening, capturing host-pathogen dynamics that are overlooked by standard in vitro assays. An administrative core fosters collaboration, manages the development and research program (DRP) to support innovative pilot projects, and liaises closely with clinical and industry advisors. By uniting modern molecular methods, computational analytics, and human- relevant models, the gladstone phaige therapy center will advance systematic, clinically ready phage therapies to combat antibiotic resistance.