Elucidation of an oral drug delivery mechanism to the mammalian gastrointestinal tract via an engineered T4 phage

Current treatments of gastrointestinal (gut) disease are limited by high dosing frequency, patient noncompliance, and complications circumventing the harsh conditions of the upper gastrointestinal tract (e.g. stomach), leading to therapeutic degradation. Bacterial cells were previously explored as vectors for biologic delivery, yet cellular engineering approaches have traditionally lowered fitness and colonization potential of these microbial factories. As a result, recombinant bacteria are often outcompeted by the native gut flora, requiring high concentrations to alleviate disease pathology. These limitations support the need for novel mechanisms of treatment that improve oral delivery compliance and ease of use. Through the research described in this dissertation, we outline the potential to use bacteriophage as an alternative chassis for biologic production and delivery to the gastrointestinal tract, targeting and reducing symptoms of obesity and ulcerative colitis. Elucidation of this system presents a universal platform for the long-term amelioration of gastrointestinal disease through the use of lytic phage particles.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biological Sciences

Department dc:contributor.department

Biological Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2025

Author dc:creator

• Baker, Zachary Robert

Chair dc:contributor.committeechair

• Hsu, Bryan

Committee members dc:contributor.committeemember

• Stevens, Ann M.
• Caswell, Clayton Christopher
• Li, Liwu

• Bacteriophage
• Intestinal microbiome
• Drug delivery
• Phage engineering
• Obesity
• Inflammatory Bowel Disease

Statement dc:rights

• Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:43391

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/132452