UC Davis

Protein biologics are a growing sector of the pharmaceutical market, demonstrating both their clinical success and their broad range of applications in health and medicine. However, there is increasing pressure to address the centralized, resource-intensive nature of conventional biomanufacturing systems. Non-traditional protein production platforms that reduce resource demands could help mitigate disparities in remote or cost-burdened health systems, strengthen global responses to emerging biological threats and disease outbreaks, and enable new approaches to health care in the context of space exploration. In this work, alternative platforms for therapeutic protein production are explored in the context of resource-limited settings, with approaches to both upstream production and downstream processing considered. We begin by exploring upstream methods to produce protein biologics in non‑traditional expression platforms. First, Chapter 3 takes an analytical approach to model multiple protein expression systems in plant hosts for supporting medicines for space health, with particular attention to constraints on mass, volume, power, and crew time. Chapter 4 then examines how plants can be used to rapidly respond to emerging biological threats, using the COVID‑19 pandemic as a case study to produce antigenic proteins for vaccines or diagnostics under tight time constraints. In Chapter 5, a particle bombardment system is used to demonstrate how a plant‑based expression platform can be adapted for mobile, decentralized deployment without the high infrastructure costs of conventional production facilities. Chapter 6 extends typical upstream processing by evaluating a low‑cost fungal expression system as a means of providing continuous access to relevant protein therapeutics during a prolonged global health emergency.To round out the analysis of these low‑resource expression modalities, downstream processing implications are considered for these applications. Chapter 7 further develops the fungal system as a viable platform for rapid, low‑cost production of therapeutics, including a large, complex glycoprotein relevant to health emergencies but notably difficult to express in traditional platforms, while Chapter 8 evaluates the system’s speed and flexibility in responding to viral mutations over the course of a pandemic. Chapter 9 turns back to plant-produced protein biologics and explores downstream processing adaptations for low‑resource scenarios, focusing on reduced reagent use, minimized processing time, and improved protein recovery from complex plant tissue lysates. Finally, Chapter 10 proposes a novel purification scheme that uses a reusable, plant‑produced affinity complex to better align downstream protein separations with consumable resource constraints.