Characterizing Phage Genomes for Therapeutic Applications.

Area of Science:

• Microbiology
• Genomics
• Drug Development

Background:

• Rising rates of multi-drug resistance necessitate novel therapeutic strategies.
• Phage therapy, using bacteriophages to treat bacterial infections, shows efficacy but lacks widespread US approval.
• A key barrier to phage therapy approval is the absence of standardized guidelines for assessing phage genomic safety.

Purpose of the Study:

• To present a comprehensive phage characterization workflow for genomic safety assessment.
• To provide essential analysis checkpoints and warnings for phage candidate submission to the Federal Drug Administration (FDA).
• To establish minimum standards for phage investigational new drug (IND) applications.

Main Methods:

• Development of a phage characterization workflow incorporating community standards for viral genome sequencing.
• Implementation of rigorous safety assessments, including quality control, exclusion of undesirable candidates, and contamination evaluation.
• Demonstration of the workflow's utility using two novel phage genomes meeting all safety criteria.

Main Results:

• The presented workflow ensures high-quality phage genomes and identifies potential safety concerns.
• Two new phage genomes were successfully characterized and met all proposed safety criteria.
• The workflow effectively assesses genomic safety and evaluates sequencing contamination.

Conclusions:

• The developed workflow provides a robust method for assessing the genomic safety of phage candidates.
• Adherence to these guidelines can facilitate the FDA review process for phage-based therapeutics.
• This proposed workflow serves as a minimum standard for phage IND submissions, paving the way for broader phage therapy adoption.